17-29630936-G-T

Variant names:

• chr17-29630936-G-T
• rs779399086
• NM_001282129.2:c.4258C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_001282129.2(SSH2):​c.4258C>A​(p.Pro1420Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,200 control chromosomes in the GnomAD database, including 1 homozygotes. 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)
  • Exomes 𝑓: 0.0000034 (1 hom.)
• Consequence: SSH2 NM_001282129.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09111726).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.4258C>A	p.Pro1420Thr	missense	Exon 16 of 16	NP_001269058.1	F5H527
	SSH2	NM_033389.3		c.4177C>A	p.Pro1393Thr	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.4258C>A	p.Pro1420Thr	missense	Exon 16 of 16	ENSP00000444743.1	F5H527
	SSH2	ENST00000269033.7	TSL:1	c.4177C>A	p.Pro1393Thr	missense	Exon 15 of 15	ENSP00000269033.3	Q76I76-1
	SSH2	ENST00000649863.1		c.4195C>A	p.Pro1399Thr	missense	Exon 14 of 14	ENSP00000497148.1	A0A3B3IS79

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251038 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1457200 Hom.: 1 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723766

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39516

South Asian (SAS) AF: 0.00 AC: 0 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1108070

Other (OTH) AF: 0.00 AC: 0 AN: 60158

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.088
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.043
Sift	Benign	0.10	T
Sift4G	Benign	0.50	T
Polyphen		0.0040	B
Vest4		0.11
MutPred		0.35		Gain of glycosylation at P1420 (P = 0.0308)
MVP		0.11
MPC		0.097
ClinPred		0.020	T
GERP RS		1.5
Varity_R		0.048
gMVP		0.13
Mutation Taster		=98/2	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

dbSNP: rs779399086; hg19: chr17-27957954;