NM_001282129.2:c.3942A>T

Variant names:

• chr17-29631252-T-A
• NM_001282129.2:c.3942A>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.3942A>T​(p.Lys1314Asn) 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: 0.655
• 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=0.15829751).

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.3942A>T	p.Lys1314Asn	missense	Exon 16 of 16	NP_001269058.1	F5H527
	SSH2	NM_033389.3		c.3861A>T	p.Lys1287Asn	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.3942A>T	p.Lys1314Asn	missense	Exon 16 of 16	ENSP00000444743.1	F5H527
	SSH2	ENST00000269033.7	TSL:1	c.3861A>T	p.Lys1287Asn	missense	Exon 15 of 15	ENSP00000269033.3	Q76I76-1
	SSH2	ENST00000649863.1		c.3879A>T	p.Lys1293Asn	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	0.22
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	0.026
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.66
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.10
Sift	Benign	0.11	T
Sift4G	Benign	0.36	T
Polyphen		0.20	B
Vest4		0.086
MutPred		0.14		Loss of ubiquitination at K1314 (P = 0.0039)
MVP		0.54
MPC		0.12
ClinPred		0.20	T
GERP RS		3.9
PromoterAI		-0.0096	Neutral
Varity_R		0.050
gMVP		0.081
Mutation Taster		=92/8	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: chr17-27958270;