rs1490097445

Variant names:

• chr17-29631203-C-A
• NM_001282129.2:c.3991G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-29631203-C-A
• chr17-29631203-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282129.2(SSH2):​c.3991G>T​(p.Asp1331Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1331E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SSH2 NM_001282129.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04764536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSH2	NM_001282129.2	c.3991G>T	p.Asp1331Tyr	missense_variant	Exon 16 of 16	ENST00000540801.6	NP_001269058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSH2	ENST00000540801.6	c.3991G>T	p.Asp1331Tyr	missense_variant	Exon 16 of 16	2	NM_001282129.2	ENSP00000444743.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461818 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727210

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.031	T;.;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.048	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.0	N;N;.
REVEL	Benign	0.071
Sift	Uncertain	0.028	D;D;.
Sift4G	Uncertain	0.039	D;D;.
Polyphen		0.0	B;B;.
Vest4		0.13
MutPred		0.11		.;Gain of phosphorylation at D1331 (P = 0.0174);.;
MVP		0.068
MPC		0.13
ClinPred		0.046	T
GERP RS		2.1
Varity_R		0.042
gMVP		0.12

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: chr17-27958221;