RPS20c.24A>GLikely benign

Print report

Variant interpretation report

RPS20 c.24A>G, p.(Lys8=)

NM_001023.4:c.24A>G NP_001014.1:p.(Lys8=) View identifiers

Classification

Likely benign

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.

Likely benign.A likely benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About RPS20

No gene-level summary was recorded for this case.

Key facts

Evidence used: 3 supporting (benign) · 1 supporting (pathogenic)
Expert rules: Not recorded
Other laboratories (ClinVar): 1 Likely benign
Pipeline record: 10 Jul 2026 · version 7.0.3

Evidence considered

View criteria

Applied evidence criteria

PM2 (supporting): This variant is present at an extremely low frequency in population databases: gnomAD v2.1 AF = 4.01e-6 (1/249,106 alleles) and v4.1 AF = 6.20e-7 (1/1,613,194 alleles), well below the 0.1% PM2 threshold. However, this is a synonymous variant with no other evidence of pathogenicity, limiting the weight of rarity alone.
BP4 (supporting): SpliceAI predicts no splice impact for this variant (max delta score = 0.00). The variant is synonymous (p.Lys8=) and is predicted not to alter splicing or protein sequence. Multiple lines of computational evidence are consistent with no functional impact.
BP6 (supporting): This variant has been reported in ClinVar as Likely benign by Ambry Genetics, a clinical testing laboratory, with criteria provided. Although from a single submitter, the classification supports a benign interpretation in the absence of any pathogenic evidence.
BP7 (supporting): This is a synonymous variant (p.Lys8=) with no predicted splice impact (SpliceAI max delta = 0.00). BP7 is met for a silent variant with no evidence of altered splicing.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.

01The reasoning

How it was classified

The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 1 Benign evidence criteria: 3

Pathogenic criteria applied · 1

PM2Supporting

PM2 · supporting

This variant is present at an extremely low frequency in population databases: gnomAD v2.1 AF = 4.01e-6 (1/249,106 alleles) and v4.1 AF = 6.20e-7 (1/1,613,194 alleles), well below the 0.1% PM2 threshold. However, this is a synonymous variant with no other evidence of pathogenicity, limiting the weight of rarity alone.

Benign criteria applied · 3

BP4Supporting

BP4 · supporting

SpliceAI predicts no splice impact for this variant (max delta score = 0.00). The variant is synonymous (p.Lys8=) and is predicted not to alter splicing or protein sequence. Multiple lines of computational evidence are consistent with no functional impact.

BP6Supporting

BP6 · supporting

This variant has been reported in ClinVar as Likely benign by Ambry Genetics, a clinical testing laboratory, with criteria provided. Although from a single submitter, the classification supports a benign interpretation in the absence of any pathogenic evidence.

BP7Supporting

BP7 · supporting

This is a synonymous variant (p.Lys8=) with no predicted splice impact (SpliceAI max delta = 0.00). BP7 is met for a silent variant with no evidence of altered splicing.

Recorded classification: Likely benign

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting benign, BP6 supporting benign, BP7 supporting benign; combination = 1 supporting + 3 supporting benign, which maps to Likely Benign.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1

gnomAD v2.1

Population frequency

1 / 1,613,194 alleles

gnomAD v4.1: 1 / 1,613,194 alleles. Recorded AF 6.19888e-07. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.01436e-06; MAF= 0.00040%, 1/249106 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.47585e-05; MAF= 0.00648%, 1/15442 alleles, homozygotes = 0).

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

Applied · PM2 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4, BP7 → SpliceAI ↗

ClinVar submissions

1 reported laboratory submissions

1 Likely benign. ClinVar API review status: criteria provided, single submitter.

Applied · BP6 → ClinVar ↗

No screenshot for this evidence

Functional evidence

Not recorded

No standalone functional evidence summary is recorded in evidence_summary.functional.

No listed criterion applied OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

No matching record reported

This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

26 criteria with recorded statuses: 4 met · 7 not met · 11 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_001023.4:c.24A>G (p.Lys8=) is a synonymous variant in exon 2 of RPS20 with no predicted effect on splicing (SpliceAI max delta = 0.00).

This variant has been classified as Likely benign in ClinVar by a single clinical laboratory (Ambry Genetics, criteria provided; variation ID 2488528).

The variant is present at extremely low frequency in population databases (gnomAD v2.1: 1/249,106 alleles, AF = 0.0004%; v4.1: 1/1,613,194 alleles, AF = 0.00006%), but rarity alone does not confer pathogenicity for a synonymous change with no functional consequence.

No functional studies, case-control data, de novo reports, segregation data, or publications mentioning this specific variant were identified.

Three supporting benign criteria are met: BP4 (computational evidence predicts no impact), BP6 (reputable source reports as benign), and BP7 (synonymous variant with no splice effect). This is consistent with a Likely benign classification per ACMG/AMP 2015 guidelines.

Met · 4

PM2 SupportingThis variant is present at an extremely low frequency in population databases: gnomAD v2.1 AF = 4.01e-6 (1/249,106 alleles) and v4.1 AF = 6.20e-7 (1/1,613,194 alleles), well below the 0.1% PM2 threshold. However, this is a synonymous variant with no other evidence of pathogenicity, limiting the weight of rarity alone. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: 1 allele in 249
106 (AF = 0.0004%)
gnomAD v4.1: 1 allele in 1
613
194 (AF = 0.00006%)
Absent from gnomAD-Canada v1.0

Sources

gnomad_v2 ↗gnomad_v4 ↗

BP4 SupportingSpliceAI predicts no splice impact for this variant (max delta score = 0.00). The variant is synonymous (p.Lys8=) and is predicted not to alter splicing or protein sequence. Multiple lines of computational evidence are consistent with no functional impact. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.00 (no donor gain
donor loss
acceptor gain
or acceptor loss predicted)
Synonymous amino acid change (p.Lys8=) — no alteration to protein sequence

Sources

spliceai ↗

BP6 SupportingThis variant has been reported in ClinVar as Likely benign by Ambry Genetics, a clinical testing laboratory, with criteria provided. Although from a single submitter, the classification supports a benign interpretation in the absence of any pathogenic evidence. Details ▾Hide ▴

Evidence considered

ClinVar variation ID 2488528: Likely benign (Ambry Genetics
criteria provided
single submitter)

Sources

clinvar ↗

BP7 SupportingThis is a synonymous variant (p.Lys8=) with no predicted splice impact (SpliceAI max delta = 0.00). BP7 is met for a silent variant with no evidence of altered splicing. Details ▾Hide ▴

Evidence considered

Synonymous substitution: NP_001014.1:p.(Lys8=)
SpliceAI max delta = 0.00 — no predicted splice alteration
Variant is not in a highly conserved nucleotide position with evidence of splicing effect

Sources

spliceai ↗

Not met · 7 · evaluated, threshold not reached

PS1 No alternative nucleotide change at c.24 resulting in the same amino acid (p.Lys8=) has been reported as pathogenic. This is a synonymous variant; there is no known pathogenic comparator with the same protein consequence. Details ▾Hide ▴

Evidence considered

ClinVar record 2488528 contains only this variant as Likely benign
no alternative pathogenic nucleotide change at this position with the same amino acid is known

Sources

clinvar ↗

PS3 No functional studies have been identified for this variant. No variant-specific or systematic range characterization (tiling screen, saturation mutagenesis, truncation series) includes NM_001023.4:c.24A>G. Details ▾Hide ▴

Evidence considered

Literature search yielded no functional data for this variant

Still missing

No functional assays have tested this variant directly or within a systematically characterized range

PM1 This variant is not located in a statistically significant mutational hotspot (cancerhotspots.org negative), and as a synonymous variant (p.Lys8=) it does not alter any amino acid residue in a critical functional domain. Details ▾Hide ▴

Evidence considered

Not present in cancerhotspots.org significant residue list
Synonymous change does not disrupt any functional domain at the protein level

PP3 No in silico predictors suggest a deleterious effect. REVEL and BayesDel scores are unavailable for this synonymous variant. SpliceAI predicts no splice impact (max delta = 0.00). No computational evidence supports pathogenicity. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.00 (no predicted splice alteration)
REVEL and BayesDel not scored (synonymous variant not evaluated by missense-based predictors)
HCI prior not available for RPS20

Sources

spliceai ↗

PP5 ClinVar classifies this variant as Likely benign, not pathogenic. No reputable source has reported it as pathogenic. Details ▾Hide ▴

Evidence considered

ClinVar variation ID 2488528: Likely benign (1 submitter
criteria provided)

Sources

clinvar ↗

BA1 The maximum allele frequency in gnomAD is 4.01e-6 (0.0004%), far below the 1% BA1 threshold. This variant is not a common polymorphism. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF = 0.0004%
gnomAD v4.1 AF = 0.00006%

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 The maximum allele frequency in gnomAD is 4.01e-6 (0.0004%), well below the 0.3% BS1 threshold. Population frequency does not support a benign classification via BS1. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF = 0.0004%
gnomAD v4.1 AF = 0.00006%

Sources

gnomad_v2 ↗gnomad_v4 ↗

Not assessed · 11 · no assessment recorded

PS2 No de novo data are available. No publications or clinical reports for this variant include de novo confirmation with parental testing. Details ▾Hide ▴

Still missing

No de novo studies or trio data available

PS4 No case-control or cohort data comparing variant prevalence in affected versus unaffected individuals are available. Details ▾Hide ▴

Still missing

No case-control studies available

PM6 No de novo data are available. No publications report de novo occurrence of this variant with confirmed maternity and paternity. Details ▾Hide ▴

Still missing

No de novo confirmation data available

PP1 No co-segregation data are available. No family studies have been reported for this variant. Details ▾Hide ▴

Still missing

No family segregation data available

PP4 No patient phenotype or clinical data are available to assess whether the presentation is highly specific for an RPS20-related disorder. Details ▾Hide ▴

Still missing

No clinical phenotype data available

BS2 No data are available regarding observation of this variant in healthy adults with full penetrance expected at their age. Details ▾Hide ▴

Still missing

No data on healthy adult carriers

BS3 No well-established functional studies have evaluated this variant for a deleterious effect. No functional data are available. Details ▾Hide ▴

Still missing

No functional studies available

BS4 No segregation data are available to assess lack of co-segregation with disease. Details ▾Hide ▴

Still missing

No family segregation data available

BP2 No data are available regarding observation of this variant in trans with a known pathogenic variant. Details ▾Hide ▴

Still missing

No trans-phase data available

BP5 No data are available regarding an alternative molecular basis for disease in a case harboring this variant. Details ▾Hide ▴

Still missing

No data on alternative molecular diagnoses in carriers

PS5 No data available to assess this criterion. No validated functional assay or established pathogenic comparator at the same position has been identified for this synonymous variant. Details ▾Hide ▴

Still missing

No data available

Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/AThis is a synonymous variant (NP_001014.1:p.(Lys8=)). PVS1 applies only to null variants (nonsense, frameshift, canonical splice ±1,2, initiation codon, single/multi-exon deletion); a silent substitution does not qualify. Details ▾Hide ▴

Evidence considered

Protein consequence is p.(Lys8=)
confirming no amino acid change
Variant does not fall into any ClinGen SVI PVS1 null-variant bucket (PMC6185798)

Sources

pvs1_generic_framework ↗

PM5 N/AThis is a synonymous variant (p.Lys8=), not a missense change. PM5 requires a different missense variant at the same residue previously classified as pathogenic. Details ▾Hide ▴

No further detail was recorded.

PP2 N/AThis is a synonymous variant, not a missense change. PP2 applies only to missense variants in genes with a low rate of benign missense variation. Details ▾Hide ▴

No further detail was recorded.

BP1 N/AThis is a synonymous variant, not a missense change. BP1 applies only to missense variants in genes where primarily truncating variants cause disease. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene: RPS20
Transcript: NM_001023.4
Coding (HGVS c.): NM_001023.4:c.24A>G
Protein (HGVS p.): NP_001014.1:p.(Lys8=)
GRCh38: chr8:56074139 T>C
GRCh37: chr8:56986698 T>C
ClinVar: 2488528

Gene diagram

Every interpreted variant in RPS20, mapped onto the exon structure of NM_001023.4. Select a row to find it on the plot.

RPS20NM_001023.4

Fetching transcript structure from UCSC…

Exons

—

Transcript span

—

Strand

—

Variants mapped

—

Source

UCSC ncbiRefSeqCurated

All variants in RPS20 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 1 / 1,613,194 alleles AF 6.2e-07 · 0 homozygotes

gnomAD v2.1 1 / 249,106 alleles AF 4.01e-06 · 0 homozygotes

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 6.2e-07 · 1 / 1,613,194 alleles · 0 hom

European (non-Finnish)1 / 1,179,910

8.5e-07

0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.

gnomAD v2.1

AF 4e-06 · 1 / 249,106 alleles · 0 hom

African/African American1 / 15,442

6.5e-05

0 alternate alleles recorded in 7 other groups: Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 6.19888e-07; MAF= 0.00006%, 1/1613194 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.47522e-07; MAF= 0.00008%, 1/1179910 alleles, homozygotes = 0).

gnomAD v2.1

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown

-0.000

Pangolin splice gain

0.010

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

SpliceAI max delta = 0.00 (no donor gain
donor loss
acceptor gain
or acceptor loss predicted)
Synonymous amino acid change (p.Lys8=) — no alteration to protein sequence

Sources

spliceai ↗

Evidence considered

Synonymous substitution: NP_001014.1:p.(Lys8=)
SpliceAI max delta = 0.00 — no predicted splice alteration
Variant is not in a highly conserved nucleotide position with evidence of splicing effect

Sources

spliceai ↗

Evidence considered

SpliceAI max delta = 0.00 (no predicted splice alteration)
REVEL and BayesDel not scored (synonymous variant not evaluated by missense-based predictors)
HCI prior not available for RPS20

Sources

spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 1 / 1,613,194 recorded alleles Open source ↗

gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗

SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗

ClinVar 1 Likely benign Open source ↗

COSMIC Captured COSMIC source record Open source ↗

Cancer hotspots Captured Cancer Hotspots source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

gnomAD v2.1

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Likely benign (1 clinical laboratory). (ClinVarID = 2488528)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

Somatic

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.