chr6-34425216-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:4

Conservation

PhyloP100: 4.95

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
RPS10	NM_001014.5 link	c.6G>A	p.Leu2Leu	synonymous_variant	Exon 2 of 6	ENST00000648437.1	NP_001005.1	P46783
RPS10-NUDT3	NM_001202470.3 link	c.6G>A	p.Leu2Leu	synonymous_variant	Exon 2 of 9		NP_001189399.1	A0A1W2PQS6
RPS10	NM_001203245.3 link	c.6G>A	p.Leu2Leu	synonymous_variant	Exon 2 of 6		NP_001190174.1	P46783
RPS10	NM_001204091.2 link	c.6G>A	p.Leu2Leu	synonymous_variant	Exon 2 of 6		NP_001191020.1	P46783

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS10	ENST00000648437.1 link	c.6G>A	p.Leu2Leu	synonymous_variant	Exon 2 of 6		NM_001014.5	ENSP00000497917.1		P46783
RPS10-NUDT3	ENST00000639725.1 link	c.6G>A	p.Leu2Leu	synonymous_variant	Exon 2 of 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

GnomAD2 exomes

AF:

0.000851

AC:

202

AN:

237388

AF XY:

0.000905

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 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

African (AFR)

AF:

0.0000299

AC:

AN:

33422

American (AMR)

AF:

0.0000229

AC:

AN:

43736

Ashkenazi Jewish (ASJ)

AF:

0.0000385

AC:

AN:

26000

East Asian (EAS)

AF:

0.00464

AC:

184

AN:

39654

South Asian (SAS)

AF:

0.000105

AC:

AN:

85578

European-Finnish (FIN)

AF:

0.00410

AC:

215

AN:

52392

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000217

AC:

241

AN:

1109620

Other (OTH)

AF:

0.000581

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

106

141

176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000670

AC:

102

AN:

152262

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41556

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00483

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00301

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000617

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000585

Hom.:

Bravo

AF:

0.000223

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

Sep 18, 2023

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diamond-Blackfan anemia 9

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.73

PhyloP100

4.9

PromoterAI

0.013

Neutral

(source)

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over