rs146246722

chr6-34425216-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.6G>A(p.Leu2=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000491 in 1,608,702 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (3 hom.)
• Consequence: RPS10 NM_001014.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.95

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=-0.34).
• BP6: Variant 6-34425216-C-T is Benign according to our data. Variant chr6-34425216-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 356423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 102 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS10	NM_001014.5	c.6G>A	p.Leu2=	synonymous_variant	2/6	ENST00000648437.1
RPS10-NUDT3	NM_001202470.3	c.6G>A	p.Leu2=	synonymous_variant	2/9
RPS10	NM_001203245.3	c.6G>A	p.Leu2=	synonymous_variant	2/6
RPS10	NM_001204091.2	c.6G>A	p.Leu2=	synonymous_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS10	ENST00000648437.1	c.6G>A	p.Leu2=	synonymous_variant	2/6		NM_001014.5	P1

Frequencies

GnomAD3 genomes AF: 0.000670 AC: 102 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000851 AC: 202 AN: 237388 Hom.: 1 AF XY: 0.000905 AC XY: 117 AN XY: 129326

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00475

Gnomad SAS exome AF: 0.0000676

Gnomad FIN exome AF: 0.00325

Gnomad NFE exome AF: 0.000415

Gnomad OTH exome AF: 0.000508

GnomAD4 exome AF: 0.000472 AC: 688 AN: 1456440 Hom.: 3 Cov.: 32 AF XY: 0.000478 AC XY: 346 AN XY: 724054

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000229

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.00464

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.00410

Gnomad4 NFE exome AF: 0.000217

Gnomad4 OTH exome AF: 0.000581

GnomAD4 genome AF: 0.000670 AC: 102 AN: 152262 Hom.: 0 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74448

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00483

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00301

Gnomad4 NFE AF: 0.000617

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000585 Hom.: 0

Bravo AF: 0.000223

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Diamond-Blackfan anemia Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 08, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Sep 18, 2023	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. -

Diamond-Blackfan anemia 9 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	15
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs146246722; hg19: chr6-34392993; COSMIC: COSV58242277; COSMIC: COSV58242277;