Variant 12-108788995-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018984.4(SSH1):c.2143C>G(p.Leu715Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00449 in 1,609,696 control chromosomes in the GnomAD database, including 302 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.025 ( 171 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 131 hom. )

Consequence

SSH1
NM_018984.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

SSH1 (HGNC:30579): (slingshot protein phosphatase 1) The protein encoded by this gene belongs to the slingshot homolog (SSH) family of phosphatases, which regulate actin filament dynamics. The SSH proteins dephosphorylate and activate the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Cofilin is inactivated by kinases such as LIM domain kinase-1 (LIMK1), which may also be dephosphorylated and inactivated by SSH proteins. The SSH family thus appears to play a role in actin dynamics by reactivating cofilin proteins. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

SSH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020462275).

BP6

Variant 12-108788995-G-C is Benign according to our data. Variant chr12-108788995-G-C is described in ClinVar as [Benign]. Clinvar id is 776749.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSH1	NM_018984.4 linkuse as main transcript	c.2143C>G	p.Leu715Val	missense_variant	15/15	ENST00000326495.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSH1	ENST00000326495.10 linkuse as main transcript	c.2143C>G	p.Leu715Val	missense_variant	15/15	1	NM_018984.4	P2	Q8WYL5-1
SSH1	ENST00000546433.5 linkuse as main transcript	c.*1136C>G		3_prime_UTR_variant, NMD_transcript_variant	7/7	5

Frequencies

GnomAD3 genomes

AF:

0.0248

AC:

3771

AN:

152140

Hom.:

171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0872

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0168

GnomAD3 exomes

AF:

0.00612

AC:

1526

AN:

249484

Hom.:

AF XY:

0.00439

AC XY:

592

AN XY:

134934

show subpopulations

Gnomad AFR exome

AF:

0.0852

Gnomad AMR exome

AF:

0.00316

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00297

GnomAD4 exome

AF:

0.00238

AC:

3465

AN:

1457438

Hom.:

131

Cov.:

AF XY:

0.00204

AC XY:

1477

AN XY:

724414

show subpopulations

Gnomad4 AFR exome

AF:

0.0857

Gnomad4 AMR exome

AF:

0.00359

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000105

Gnomad4 OTH exome

AF:

0.00512

GnomAD4 genome

AF:

0.0248

AC:

3769

AN:

152258

Hom.:

171

Cov.:

AF XY:

0.0233

AC XY:

1737

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0869

Gnomad4 AMR

AF:

0.00680

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.00346

Hom.:

Bravo

AF:

0.0277

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0828

AC:

365

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00766

AC:

930

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.71

Cadd

Benign

9.3

Dann

Benign

0.93

DEOGEN2

Benign

0.067

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.53

REVEL

Benign

0.11

Sift

Uncertain

0.0070

Sift4G

Benign

0.41

Polyphen

0.36

Vest4

0.068

MVP

0.16

MPC

0.37

ClinPred

0.025

GERP RS

4.1

Varity_R

0.088

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over