Variant 3-156543249-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007107.5(SSR3):c.512G>A(p.Ser171Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SSR3
NM_007107.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66

Variant links:

Genes affected

SSR3 (HGNC:11325): (signal sequence receptor subunit 3) The signal sequence receptor (SSR) is a glycosylated endoplasmic reticulum (ER) membrane receptor associated with protein translocation across the ER membrane. The SSR is comprised of four membrane proteins/subunits: alpha, beta, gamma, and delta. The first two are glycosylated subunits and the latter two are non-glycosylated subunits. This gene encodes the gamma subunit, which is predicted to span the membrane four times. [provided by RefSeq, Aug 2010]

SSR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSR3	NM_007107.5 link	c.512G>A	p.Ser171Asn	missense_variant	Exon 5 of 5	ENST00000265044.7	NP_009038.1	Q9UNL2-1
SSR3	NM_001308197.2 link	c.551G>A	p.Ser184Asn	missense_variant	Exon 5 of 5		NP_001295126.1	Q9UNL2-2
SSR3	NM_001308204.2 link	c.356G>A	p.Ser119Asn	missense_variant	Exon 5 of 5		NP_001295133.1	Q9UNL2C9J365
SSR3	NM_001308205.2 link	c.356G>A	p.Ser119Asn	missense_variant	Exon 5 of 5		NP_001295134.1	Q9UNL2C9J365

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSR3	ENST00000265044.7 link	c.512G>A	p.Ser171Asn	missense_variant	Exon 5 of 5	1	NM_007107.5	ENSP00000265044.2		Q9UNL2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251316

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135838

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461568

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 07, 2024

This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 184 of the SSR3 protein (p.Ser184Asn). This variant is present in population databases (rs754178019, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SSR3-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.;T;T

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.81

T;T;.;T

M_CAP

Benign

0.0033

MetaRNN

Uncertain

0.52

D;D;D;D

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

N;.;.;.

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.084

Sift

Benign

0.13

T;T;T;T

Sift4G

Benign

0.23

T;T;T;T

Polyphen

0.18

B;.;.;.

Vest4

0.61

MutPred

0.56

.;Loss of glycosylation at S187 (P = 0.0309);.;.;

MVP

0.63

MPC

0.55

ClinPred

0.72

GERP RS

5.4

Varity_R

0.31

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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