3-156548916-C-G

Position:

• chr3-156548916-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007107.5(SSR3):​c.348G>C​(p.Glu116Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SSR3 NM_007107.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.65

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36497945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSR3	NM_007107.5	c.348G>C	p.Glu116Asp	missense_variant	3/5	ENST00000265044.7	NP_009038.1
SSR3	NM_001308197.2	c.348G>C	p.Glu116Asp	missense_variant	3/5		NP_001295126.1
SSR3	NM_001308204.2	c.192G>C	p.Glu64Asp	missense_variant	3/5		NP_001295133.1
SSR3	NM_001308205.2	c.192G>C	p.Glu64Asp	missense_variant	3/5		NP_001295134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSR3	ENST00000265044.7	c.348G>C	p.Glu116Asp	missense_variant	3/5	1	NM_007107.5	ENSP00000265044.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 12, 2023

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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with SSR3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 116 of the SSR3 protein (p.Glu116Asp). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	0.00086	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.;T;T;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D;D;D;.;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.36	T;T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.3	M;M;.;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.2	N;N;N;N;N
REVEL	Uncertain	0.40
Sift	Benign	0.13	T;D;T;T;T
Sift4G	Benign	0.084	T;T;T;T;T
Polyphen		1.0	D;.;.;.;.
Vest4		0.57
MutPred		0.60		Gain of glycosylation at S113 (P = 0.0048);Gain of glycosylation at S113 (P = 0.0048);Gain of glycosylation at S113 (P = 0.0048);.;.;
MVP		0.47
MPC		0.92
ClinPred		0.97	D
GERP RS		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-156266705;