rs146246722

Positions:

chr6-34425216-C-T

Variant summary

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

The NM_001014.5(RPS10):c.6G>A(p.Leu2Leu) 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.95

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:

RPS10 (HGNC:):

RPS10 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=-0.34).

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 GnomAd4 at 102 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS10	NM_001014.5 linkuse as main transcript	c.6G>A	p.Leu2Leu	synonymous_variant	2/6	ENST00000648437.1	NP_001005.1	P46783
RPS10-NUDT3	NM_001202470.3 linkuse as main transcript	c.6G>A	p.Leu2Leu	synonymous_variant	2/9		NP_001189399.1	A0A1W2PQS6
RPS10	NM_001203245.3 linkuse as main transcript	c.6G>A	p.Leu2Leu	synonymous_variant	2/6		NP_001190174.1	P46783
RPS10	NM_001204091.2 linkuse as main transcript	c.6G>A	p.Leu2Leu	synonymous_variant	2/6		NP_001191020.1	P46783

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS10	ENST00000648437.1 linkuse as main transcript	c.6G>A	p.Leu2Leu	synonymous_variant	2/6		NM_001014.5	ENSP00000497917.1		P46783
RPS10-NUDT3	ENST00000639725.1 linkuse as main transcript	c.6G>A	p.Leu2Leu	synonymous_variant	2/9	5		ENSP00000492441.1		A0A1W2PQS6

Frequencies

GnomAD3 genomes

AF:

0.000670

AC:

102

AN:

152144

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.000905

AC XY:

117

AN XY:

129326

show subpopulations

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.:

Cov.:

AF XY:

0.000478

AC XY:

346

AN XY:

724054

show subpopulations

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.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74448

show subpopulations

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.:

Bravo

AF:

0.000223

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Diamond-Blackfan anemia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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

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

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