rs1490097445

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00600
Variant links:
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)

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ACMG classification

Classification made for transcript

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
SSH2NM_001282129.2 linkc.3991G>T p.Asp1331Tyr missense_variant Exon 16 of 16 ENST00000540801.6 NP_001269058.1 Q76I76F5H527B4DK64

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSH2ENST00000540801.6 linkc.3991G>T p.Asp1331Tyr missense_variant Exon 16 of 16 2 NM_001282129.2 ENSP00000444743.1 F5H527

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
show subpopulations
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; API