dbSNP rs199588276: GSKIP:p.Gly137Arg (chr14-96385673-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016472.5(GSKIP):c.409G>A(p.Gly137Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000182 in 1,611,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

GSKIP
NM_016472.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.27

Publications

3 publications found

Variant links:

Genes affected

GSKIP (HGNC:20343): (GSK3B interacting protein) This gene encodes a protein that is involved as a negative regulator of GSK3-beta in the Wnt signaling pathway. The encoded protein may play a role in the retinoic acid signaling pathway by regulating the functional interactions between GSK3-beta, beta-catenin and cyclin D1, and it regulates the beta-catenin/N-cadherin pool. The encoded protein contains a GSK3-beta interacting domain (GID) in its C-terminus, which is similar to the GID of Axin. The protein also contains an evolutionarily conserved RII-binding domain, which facilitates binding with protein kinase-A and GSK3-beta, enabling its role as an A-kinase anchoring protein. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2012]

GSKIP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.1152488).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016472.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSKIP	NM_016472.5	MANE Select	c.409G>A	p.Gly137Arg	missense	Exon 4 of 4	NP_057556.2	Q9P0R6
GSKIP	NM_001271904.1		c.409G>A	p.Gly137Arg	missense	Exon 4 of 4	NP_001258833.1	Q9P0R6
GSKIP	NM_001271905.2		c.409G>A	p.Gly137Arg	missense	Exon 4 of 4	NP_001258834.1	Q9P0R6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSKIP	ENST00000555181.6	TSL:1 MANE Select	c.409G>A	p.Gly137Arg	missense	Exon 4 of 4	ENSP00000450420.1	Q9P0R6
GSKIP	ENST00000438650.5	TSL:2	c.409G>A	p.Gly137Arg	missense	Exon 3 of 3	ENSP00000412315.1	Q9P0R6
GSKIP	ENST00000554182.5	TSL:2	c.409G>A	p.Gly137Arg	missense	Exon 4 of 4	ENSP00000451384.1	Q9P0R6

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000116

AC:

AN:

249964

AF XY:

0.0000888

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:

0.000247

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000193

AC:

281

AN:

1459692

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

130

AN XY:

726226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44560

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000245

AC:

272

AN:

1111248

Other (OTH)

AF:

0.000133

AC:

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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

AF:

0.0000789

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41390

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000152

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

0.24

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.034

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.86

M_CAP

Benign

0.0051

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.0

PhyloP100

6.3

PrimateAI

Benign

0.47

PROVEAN

Benign

0.96

REVEL

Benign

0.22

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.0070

Polyphen

0.99

Vest4

0.16

MutPred

0.22

Gain of solvent accessibility (P = 0.0037)

MVP

0.082

MPC

0.75

ClinPred

0.23

GERP RS

5.7

Varity_R

0.11

gMVP

0.49

Mutation Taster

=74/26

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over