1-156020023-C-T

Variant names:

• chr1-156020023-C-T
• NM_003145.4:c.145G>A

Variant summary

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

The NM_003145.4(SSR2):​c.145G>A​(p.Val49Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SSR2 NM_003145.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.71

Genes affected

SSR2 (HGNC:11324): (signal sequence receptor subunit 2) The signal sequence receptor (SSR) is a glycosylated endoplasmic reticulum (ER) membrane receptor associated with protein translocation across the ER membrane. The SSR consists of 2 subunits, a 34-kD glycoprotein (alpha-SSR or SSR1) and a 22-kD glycoprotein (beta-SSR or SSR2). The human beta-signal sequence receptor gene (SSR2) maps to chromosome bands 1q21-q23. [provided by RefSeq, Jul 2008]

ENSG00000285677 (HGNC:):

ACMG classification

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
SSR2	NM_003145.4	c.145G>A	p.Val49Ile	missense_variant	Exon 2 of 6	ENST00000295702.9	NP_003136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSR2	ENST00000295702.9	c.145G>A	p.Val49Ile	missense_variant	Exon 2 of 6	1	NM_003145.4	ENSP00000295702.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 16, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.145G>A (p.V49I) alteration is located in exon 2 (coding exon 1) of the SSR2 gene. This alteration results from a G to A substitution at nucleotide position 145, causing the valine (V) at amino acid position 49 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;T;T;T;T
Eigen	Benign	-0.037
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.66	D;D;D;D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L;.;.;L;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.59	N;N;N;N;N;.
REVEL	Benign	0.22
Sift	Benign	0.28	T;T;D;T;T;.
Sift4G	Benign	0.39	T;T;T;T;T;.
Polyphen		0.027	B;.;.;B;.;.
Vest4		0.57
MutPred		0.71		Gain of catalytic residue at A53 (P = 0.1876);Gain of catalytic residue at A53 (P = 0.1876);Gain of catalytic residue at A53 (P = 0.1876);Gain of catalytic residue at A53 (P = 0.1876);Gain of catalytic residue at A53 (P = 0.1876);.;
MVP		0.10
MPC		0.65
ClinPred		0.91	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.23

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: chr1-155989814;