17-29631319-T-C

Position:

• chr17-29631319-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282129.2(SSH2):​c.3875A>G​(p.Tyr1292Cys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SSH2 NM_001282129.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19

Genes affected

SSH2 (HGNC:30580): (slingshot protein phosphatase 2) This gene encodes a protein tyrosine phosphatase that plays a key role in the regulation of actin filaments. The encoded protein dephosphorylates and activates cofilin, which promotes actin filament depolymerization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ABHD15-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1109581).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSH2	NM_001282129.2	c.3875A>G	p.Tyr1292Cys	missense_variant	16/16	ENST00000540801.6	NP_001269058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSH2	ENST00000540801.6	c.3875A>G	p.Tyr1292Cys	missense_variant	16/16	2	NM_001282129.2	ENSP00000444743.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.3794A>G (p.Y1265C) alteration is located in exon 15 (coding exon 15) of the SSH2 gene. This alteration results from a A to G substitution at nucleotide position 3794, causing the tyrosine (Y) at amino acid position 1265 to be replaced by a cysteine (C). 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	0.098
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.017	T;.;.
Eigen	Benign	-0.045
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.1	N;N;.
REVEL	Benign	0.067
Sift	Benign	0.27	T;T;.
Sift4G	Benign	0.26	T;T;.
Polyphen		0.0020	B;B;.
Vest4		0.19
MutPred		0.29		.;Gain of helix (P = 0.0143);.;
MVP		0.15
MPC		0.10
ClinPred		0.38	T
GERP RS		5.1
Varity_R		0.044
gMVP		0.061

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: chr17-27958337;