17-29631287-T-A

Variant names:

• chr17-29631287-T-A
• NM_001282129.2:c.3907A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282129.2(SSH2):​c.3907A>T​(p.Arg1303Trp) 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. 15/22 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: 0.904
• Publications: 0 publications found

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:49685): (ABHD15 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13907874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282129.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSH2	NM_001282129.2	MANE Select	c.3907A>T	p.Arg1303Trp	missense	Exon 16 of 16	NP_001269058.1	F5H527
	SSH2	NM_033389.3		c.3826A>T	p.Arg1276Trp	missense	Exon 15 of 15	NP_203747.2	Q76I76-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSH2	ENST00000540801.6	TSL:2 MANE Select	c.3907A>T	p.Arg1303Trp	missense	Exon 16 of 16	ENSP00000444743.1	F5H527
	SSH2	ENST00000269033.7	TSL:1	c.3826A>T	p.Arg1276Trp	missense	Exon 15 of 15	ENSP00000269033.3	Q76I76-1
	SSH2	ENST00000649863.1		c.3844A>T	p.Arg1282Trp	missense	Exon 14 of 14	ENSP00000497148.1	A0A3B3IS79

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.0020
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.90
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.13
Sift	Benign	0.066	T
Sift4G	Benign	0.12	T
Polyphen		0.98	D
Vest4		0.20
MutPred		0.23		Loss of disorder (P = 0.0016)
MVP		0.24
MPC		0.37
ClinPred		0.46	T
GERP RS		0.95
PromoterAI		-0.0044	Neutral
Varity_R		0.044
gMVP		0.24
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chr17-27958305;