rs1363625313

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017857.4(SSH3):​c.206C>A​(p.Pro69Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,580 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. P69L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SSH3
NM_017857.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.798
Variant links:
Genes affected
SSH3 (HGNC:30581): (slingshot protein phosphatase 3) The ADF (actin-depolymerizing factor)/cofilin family (see MIM 601442) is composed of stimulus-responsive mediators of actin dynamics. ADF/cofilin proteins are inactivated by kinases such as LIM domain kinase-1 (LIMK1; MIM 601329). The SSH family appears to play a role in actin dynamics by reactivating ADF/cofilin proteins in vivo (Niwa et al., 2002 [PubMed 11832213]).[supplied by OMIM, Mar 2008]

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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=0.06709546).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSH3NM_017857.4 linkc.206C>A p.Pro69Gln missense_variant Exon 3 of 14 ENST00000308127.9 NP_060327.3 Q8TE77-1A0A024R5J4
SSH3XM_047427177.1 linkc.206C>A p.Pro69Gln missense_variant Exon 3 of 13 XP_047283133.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSH3ENST00000308127.9 linkc.206C>A p.Pro69Gln missense_variant Exon 3 of 14 1 NM_017857.4 ENSP00000312081.4 Q8TE77-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461580
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727080
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
3.0
DANN
Benign
0.81
DEOGEN2
Benign
0.077
T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.31
T;T
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.067
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.41
N;.
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.012
Sift
Uncertain
0.022
D;T
Sift4G
Benign
0.70
T;T
Polyphen
0.0050
B;.
Vest4
0.15
MutPred
0.17
Loss of glycosylation at P69 (P = 0.0471);Loss of glycosylation at P69 (P = 0.0471);
MVP
0.072
MPC
0.16
ClinPred
0.040
T
GERP RS
-1.2
Varity_R
0.034
gMVP
0.25

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: chr11-67072345; COSMIC: COSV100354885; COSMIC: COSV100354885; API