17-29631794-G-C

Variant names:

• chr17-29631794-G-C
• NM_001282129.2:c.3400C>G

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.3400C>G​(p.Leu1134Val) 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. 16/22 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: 0.414
• 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=0.07346466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSH2	NM_001282129.2	c.3400C>G	p.Leu1134Val	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.3400C>G	p.Leu1134Val	missense_variant	Exon 16 of 16	2	NM_001282129.2	ENSP00000444743.1
SSH2	ENST00000269033.7	c.3319C>G	p.Leu1107Val	missense_variant	Exon 15 of 15	1		ENSP00000269033.3
SSH2	ENST00000649863.1	c.3337C>G	p.Leu1113Val	missense_variant	Exon 14 of 14			ENSP00000497148.1
ABHD15-AS1	ENST00000581474.1	n.153+71095G>C		intron_variant	Intron 1 of 1	5

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

Dec 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3319C>G (p.L1107V) alteration is located in exon 15 (coding exon 15) of the SSH2 gene. This alteration results from a C to G substitution at nucleotide position 3319, causing the leucine (L) at amino acid position 1107 to be replaced by a valine (V). 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	0.074
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.5
DANN	Benign	0.67
DEOGEN2	Benign	0.022	T;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.073	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N;.;.
PhyloP100		0.41
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.010	N;N;.
REVEL	Benign	0.11
Sift	Benign	0.20	T;T;.
Sift4G	Benign	1.0	T;T;.
Polyphen		0.023	B;B;.
Vest4		0.0060
MutPred		0.028		.;Gain of glycosylation at S1135 (P = 0.0932);.;
MVP		0.15
MPC		0.092
ClinPred		0.11	T
GERP RS		4.9
PromoterAI		-0.020	Neutral
Varity_R		0.030
gMVP		0.12
Mutation Taster		=89/11	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: chr17-27958812;