Genetic Variant SSH3:p.Pro11Ser (chr11-67303656-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017857.4(SSH3):c.31C>T(p.Pro11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,360,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P11L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SSH3
NM_017857.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.504

Publications

0 publications found

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]

SSH3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03548947).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017857.4. 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
	SSH3	NM_017857.4	MANE Select	c.31C>T	p.Pro11Ser	missense	Exon 1 of 14	NP_060327.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSH3	ENST00000308127.9	TSL:1 MANE Select	c.31C>T	p.Pro11Ser	missense	Exon 1 of 14	ENSP00000312081.4	Q8TE77-1
SSH3	ENST00000532881.5	TSL:1	n.31C>T		non_coding_transcript_exon	Exon 1 of 14	ENSP00000431788.2	Q8TE77-2
SSH3	ENST00000882806.1		c.31C>T	p.Pro11Ser	missense	Exon 1 of 14	ENSP00000552865.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000928

AC:

AN:

107782

AF XY:

0.000150

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000162

AC:

AN:

1360792

Hom.:

Cov.:

AF XY:

0.0000238

AC XY:

AN XY:

671432

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28030

American (AMR)

AF:

0.00

AC:

AN:

34122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24220

East Asian (EAS)

AF:

0.00

AC:

AN:

32482

South Asian (SAS)

AF:

0.000259

AC:

AN:

77144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4840

European-Non Finnish (NFE)

AF:

9.35e-7

AC:

AN:

1069268

Other (OTH)

AF:

0.0000176

AC:

AN:

56808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000516

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

0.067

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

PhyloP100

0.50

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.40

REVEL

Benign

0.048

Sift

Benign

0.36

Sift4G

Benign

0.77

Polyphen

0.025

Vest4

0.11

MutPred

0.14

Gain of phosphorylation at P11 (P = 0.0119)

MVP

0.20

MPC

0.17

ClinPred

0.029

GERP RS

3.0

PromoterAI

0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.11

gMVP

0.22

Mutation Taster

=94/6

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