chr6-34424760-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_001014.5(RPS10):c.231G>A(p.Gln77Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.00204 in 1,614,136 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 7 hom. )

Consequence

RPS10
NM_001014.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.98

Variant links:

Genes affected

RPS10 (HGNC:10383): (ribosomal protein S10) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S10E family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternate splicing results in multiple transcript variants that encode the same protein. Naturally occurring read-through transcription occurs between this locus and the neighboring locus NUDT3 (nudix (nucleoside diphosphate linked moiety X)-type motif 3).[provided by RefSeq, Feb 2011]

RPS10 links:

RPS10-NUDT3 (HGNC:49181): (RPS10-NUDT3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring RPS10 (ribosomal protein S10) and NUDT3 (nudix (nucleoside diphosphate linked moiety X)-type motif 3) genes on chromosome 6. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

RPS10-NUDT3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 6-34424760-C-T is Benign according to our data. Variant chr6-34424760-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 238211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-34424760-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 187 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS10	NM_001014.5 link	c.231G>A	p.Gln77Gln	synonymous_variant	Exon 3 of 6	ENST00000648437.1	NP_001005.1	P46783
RPS10-NUDT3	NM_001202470.3 link	c.231G>A	p.Gln77Gln	synonymous_variant	Exon 3 of 9		NP_001189399.1	A0A1W2PQS6
RPS10	NM_001203245.3 link	c.231G>A	p.Gln77Gln	synonymous_variant	Exon 3 of 6		NP_001190174.1	P46783
RPS10	NM_001204091.2 link	c.231G>A	p.Gln77Gln	synonymous_variant	Exon 3 of 6		NP_001191020.1	P46783

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS10	ENST00000648437.1 link	c.231G>A	p.Gln77Gln	synonymous_variant	Exon 3 of 6		NM_001014.5	ENSP00000497917.1		P46783
RPS10-NUDT3	ENST00000639725.1 link	c.231G>A	p.Gln77Gln	synonymous_variant	Exon 3 of 9	5		ENSP00000492441.1		A0A1W2PQS6

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

188

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00188

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00167

AC:

418

AN:

250462

Hom.:

AF XY:

0.00166

AC XY:

225

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.000439

Gnomad AMR exome

AF:

0.000666

Gnomad ASJ exome

AF:

0.00368

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000850

Gnomad FIN exome

AF:

0.000556

Gnomad NFE exome

AF:

0.00268

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00213

AC:

3109

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1535

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000788

Gnomad4 FIN exome

AF:

0.000806

Gnomad4 NFE exome

AF:

0.00247

Gnomad4 OTH exome

AF:

0.00210

GnomAD4 genome

AF:

0.00123

AC:

187

AN:

152322

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00188

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00205

Hom.:

Bravo

AF:

0.00116

EpiCase

AF:

0.00169

EpiControl

AF:

0.00154

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Diamond-Blackfan anemia

Benign:2

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 06, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not specified

Benign:1

Oct 04, 2019

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diamond-Blackfan anemia 9

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over