Genetic Variant SSH1:p.Ala885Thr (chr12-108788485-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018984.4(SSH1):c.2653G>A(p.Ala885Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,403,338 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SSH1
NM_018984.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.063358724).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018984.4. 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
	SSH1	NM_018984.4	MANE Select	c.2653G>A	p.Ala885Thr	missense	Exon 15 of 15	NP_061857.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSH1	ENST00000326495.10	TSL:1 MANE Select	c.2653G>A	p.Ala885Thr	missense	Exon 15 of 15	ENSP00000315713.5	Q8WYL5-1
SSH1	ENST00000877978.1		c.2584G>A	p.Ala862Thr	missense	Exon 14 of 14	ENSP00000548037.1
SSH1	ENST00000546433.5	TSL:5	n.*1646G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000447629.1	H0YHR3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000201

AC:

AN:

199472

AF XY:

0.0000282

show subpopulations

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:

0.0000426

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1403338

Hom.:

Cov.:

AF XY:

0.0000246

AC XY:

AN XY:

692340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31396

American (AMR)

AF:

0.00

AC:

AN:

36004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21926

East Asian (EAS)

AF:

0.00

AC:

AN:

39290

South Asian (SAS)

AF:

0.00

AC:

AN:

75612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5470

European-Non Finnish (NFE)

AF:

0.0000230

AC:

AN:

1085530

Other (OTH)

AF:

0.0000347

AC:

AN:

57700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000509

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.2

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.033

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.59

M_CAP

Benign

0.0028

MetaRNN

Benign

0.063

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

PhyloP100

1.7

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.10

REVEL

Benign

0.079

Sift

Benign

0.27

Sift4G

Benign

0.53

Polyphen

0.0010

Vest4

0.085

MutPred

0.15

Gain of glycosylation at A885 (P = 0.0038)

MVP

0.36

MPC

0.29

ClinPred

0.080

GERP RS

0.72

Varity_R

0.029

gMVP

0.22

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over