Variant 11-126265036-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003139.4(SRPRA):c.1448G>A(p.Gly483Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0098 in 1,614,186 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 5 hom., cov: 33)

Exomes 𝑓: 0.010 ( 93 hom. )

Consequence

SRPRA
NM_003139.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 7.54

Variant links:

Genes affected

SRPRA (HGNC:11307): (SRP receptor subunit alpha) The gene encodes a subunit of the endoplasmic reticulum signal recognition particle receptor that, in conjunction with the signal recognition particle, is involved in the targeting and translocation of signal sequence tagged secretory and membrane proteins across the endoplasmic reticulum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

SRPRA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010002643).

BP6

Variant 11-126265036-C-T is Benign according to our data. Variant chr11-126265036-C-T is described in ClinVar as [Benign]. Clinvar id is 2642522.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 915 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPRA	NM_003139.4 link	c.1448G>A	p.Gly483Asp	missense_variant	11/14	ENST00000332118.11	NP_003130.2	P08240-1
SRPRA	NM_001177842.2 link	c.1364G>A	p.Gly455Asp	missense_variant	10/13		NP_001171313.1	P08240-2
SRPRA	XM_047427497.1 link	c.1448G>A	p.Gly483Asp	missense_variant	11/14		XP_047283453.1
SRPRA	XM_017018179.3 link	c.1448G>A	p.Gly483Asp	missense_variant	11/14		XP_016873668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SRPRA	ENST00000332118.11 link	c.1448G>A	p.Gly483Asp	missense_variant	11/14	1	NM_003139.4	ENSP00000328023.5	P08240-1
SRPRA	ENST00000532259.1 link	c.1364G>A	p.Gly455Asp	missense_variant	10/13	2		ENSP00000435508.1	P08240-2
SRPRA	ENST00000531104.1 link	n.527G>A		non_coding_transcript_exon_variant	2/2	2
SRPRA	ENST00000527817.1 link	n.*44G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00601

AC:

915

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00528

AC:

1327

AN:

251404

Hom.:

AF XY:

0.00530

AC XY:

720

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00360

Gnomad NFE exome

AF:

0.00982

Gnomad OTH exome

AF:

0.00537

GnomAD4 exome

AF:

0.0102

AC:

14904

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00991

AC XY:

7206

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.00491

Gnomad4 NFE exome

AF:

0.0125

Gnomad4 OTH exome

AF:

0.00848

GnomAD4 genome

AF:

0.00601

AC:

915

AN:

152326

Hom.:

Cov.:

AF XY:

0.00503

AC XY:

375

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00938

Hom.:

Bravo

AF:

0.00574

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0174

AC:

ESP6500AA

AF:

0.00273

AC:

ESP6500EA

AF:

0.0122

AC:

105

ExAC

AF:

0.00504

AC:

612

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00949

EpiControl

AF:

0.00925

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

SRPRA: BS1, BS2 -

SRPRA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2020

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

Benign

0.18

BayesDel_addAF

Uncertain

0.064

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.67

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.37

Sift

Benign

0.047

D;D

Sift4G

Benign

0.10

T;T

Polyphen

0.38

B;.

Vest4

0.83

MVP

0.64

MPC

1.4

ClinPred

0.033

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.65

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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