Variant rs371964689 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000458500.5(RPL10):c.470C>T(p.Pro157Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000599 in 1,209,786 control chromosomes in the GnomAD database, including 3 homozygotes. There are 333 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., 10 hem., cov: 23)

Exomes 𝑓: 0.00063 ( 3 hom. 323 hem. )

Consequence

RPL10
ENST00000458500.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0510

Variant links:

Genes affected

RPL10 (HGNC:10298): (ribosomal protein L10) This gene encodes a ribosomal protein that is a component of the 60S ribosome subunit. The related protein in chicken can bind to c-Jun and can repress c-Jun-mediated transcriptional activation. Some studies have detected an association between variation in this gene and autism spectrum disorders, though others do not detect this relationship. There are multiple pseudogenes of this gene dispersed throughout the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

RPL10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008334637).

BP6

Variant X-154400842-C-T is Benign according to our data. Variant chrX-154400842-C-T is described in ClinVar as [Benign]. Clinvar id is 589527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-154400842-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL10	NM_006013.5 linkuse as main transcript	c.633C>T	p.Ala211=	synonymous_variant	7/7	ENST00000369817.7	NP_006004.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL10	ENST00000369817.7 linkuse as main transcript	c.633C>T	p.Ala211=	synonymous_variant	7/7	5	NM_006013.5	ENSP00000358832	P1

Frequencies

GnomAD3 genomes

AF:

0.000285

AC:

AN:

112280

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

AN XY:

34434

show subpopulations

Gnomad AFR

AF:

0.000130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000188

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00839

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00131

GnomAD3 exomes

AF:

0.00179

AC:

303

AN:

169742

Hom.:

AF XY:

0.00274

AC XY:

159

AN XY:

57948

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0161

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000678

Gnomad OTH exome

AF:

0.00141

GnomAD4 exome

AF:

0.000631

AC:

693

AN:

1097453

Hom.:

Cov.:

AF XY:

0.000890

AC XY:

323

AN XY:

362901

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0112

Gnomad4 FIN exome

AF:

0.0000249

Gnomad4 NFE exome

AF:

0.0000321

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.000285

AC:

AN:

112333

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

AN XY:

34497

show subpopulations

Gnomad4 AFR

AF:

0.000130

Gnomad4 AMR

AF:

0.000187

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00842

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00130

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000162

ExAC

AF:

0.00217

AC:

262

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 16, 2014

This alteration is classified as 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 provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.5

DANN

Uncertain

1.0

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0083

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Benign

-0.63

REVEL

Benign

0.083

Sift

Benign

0.053

Sift4G

Benign

0.16

Polyphen

0.0010

MutPred

0.36

Loss of loop (P = 0.0128);

MVP

0.45

ClinPred

0.022

GERP RS

-0.68

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