Variant 3-158123954-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_001271838.2(RSRC1):c.283A>G(p.Arg95Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000535 in 1,612,260 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 4 hom. )

Consequence

RSRC1
NM_001271838.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.85

Variant links:

Genes affected

RSRC1 (HGNC:24152): (arginine and serine rich coiled-coil 1) This gene encodes a member of the serine and arginine rich-related protein family. The encoded protein is involved in both constitutive and alternative mRNA splicing. This gene may be associated with schizophrenia. A pseudogene of this gene is located on chromosome 9. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

RSRC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074111223).

BP6

Variant 3-158123954-A-G is Benign according to our data. Variant chr3-158123954-A-G is described in ClinVar as [Benign]. Clinvar id is 3035452.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000381 (58/152236) while in subpopulation NFE AF= 0.000353 (24/68034). AF 95% confidence interval is 0.000243. There are 1 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSRC1	NM_001271838.2 linkuse as main transcript	c.283A>G	p.Arg95Gly	missense_variant	3/10	ENST00000611884.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSRC1	ENST00000611884.5 linkuse as main transcript	c.283A>G	p.Arg95Gly	missense_variant	3/10	5	NM_001271838.2	P4	Q96IZ7-1

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000494

AC:

124

AN:

251218

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00765

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000551

AC:

804

AN:

1460024

Hom.:

Cov.:

AF XY:

0.000556

AC XY:

404

AN XY:

726356

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00836

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000473

Gnomad4 OTH exome

AF:

0.000962

GnomAD4 genome

AF:

0.000381

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000772

Hom.:

Bravo

AF:

0.000389

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000346

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RSRC1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.16

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.21

T;T;T;T;T;.;.;T;T

Eigen

Benign

-0.022

Eigen_PC

Benign

0.015

FATHMM_MKL

Uncertain

0.79

M_CAP

Benign

0.010

MetaRNN

Benign

0.0074

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

L;.;L;L;.;L;L;.;.

MutationTaster

Benign

0.97

D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.8

D;D;.;D;D;D;D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0030

D;D;.;D;D;D;D;D;D

Sift4G

Uncertain

0.018

D;T;D;D;T;D;D;D;T

Polyphen

0.88

P;.;P;P;.;P;P;.;.

Vest4

0.53

MVP

0.70

MPC

0.095

ClinPred

0.11

GERP RS

2.5

Varity_R

0.36

gMVP

0.33

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