rs147863199

chr6-34424760-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001014.5(RPS10):c.231G>A(p.Gln77=) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.98

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-NUDT3 (HGNC:):

ACMG classification

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 GnomAd at 188 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS10	NM_001014.5	c.231G>A	p.Gln77=	synonymous_variant	3/6	ENST00000648437.1
RPS10-NUDT3	NM_001202470.3	c.231G>A	p.Gln77=	synonymous_variant	3/9
RPS10	NM_001203245.3	c.231G>A	p.Gln77=	synonymous_variant	3/6
RPS10	NM_001204091.2	c.231G>A	p.Gln77=	synonymous_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS10	ENST00000648437.1	c.231G>A	p.Gln77=	synonymous_variant	3/6		NM_001014.5	P1

Frequencies

GnomAD3 genomes AF: 0.00124 AC: 188 AN: 152204 Hom.: 0 Cov.: 32

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.: 3 AF XY: 0.00166 AC XY: 225 AN XY: 135638

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.: 7 Cov.: 31 AF XY: 0.00211 AC XY: 1535 AN XY: 727212

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.: 0 Cov.: 32 AF XY: 0.00102 AC XY: 76 AN XY: 74482

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.: 0

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

Submissions by phenotype

Diamond-Blackfan anemia Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 06, 2022	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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 26, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 04, 2019

- -

Diamond-Blackfan anemia 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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	13
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

Other links and lift over

dbSNP: rs147863199; hg19: chr6-34392537;