Variant 14-96382429-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016472.5(GSKIP):c.182A>C(p.Asp61Ala) 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 1,461,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.0000014 ( 0 hom. )

Consequence

GSKIP
NM_016472.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.57

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0797379).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GSKIP	NM_016472.5 linkuse as main transcript	c.182A>C	p.Asp61Ala	missense_variant	3/4	ENST00000555181.6
GSKIP	NM_001271904.1 linkuse as main transcript	c.182A>C	p.Asp61Ala	missense_variant	3/4
GSKIP	NM_001271905.2 linkuse as main transcript	c.182A>C	p.Asp61Ala	missense_variant	3/4
GSKIP	NM_001271906.2 linkuse as main transcript	c.182A>C	p.Asp61Ala	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSKIP	ENST00000555181.6 linkuse as main transcript	c.182A>C	p.Asp61Ala	missense_variant	3/4	1	NM_016472.5	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461082

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.182A>C (p.D61A) alteration is located in exon 2 (coding exon 1) of the GSKIP gene. This alteration results from a A to C substitution at nucleotide position 182, causing the aspartic acid (D) at amino acid position 61 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.19

T;T;.;T;T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.83

T;.;T;.;.;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.080

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.58

N;N;.;N;N;.

MutationTaster

Benign

0.95

N;N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.1

N;N;D;N;N;D

REVEL

Benign

0.047

Sift

Benign

0.79

T;T;T;T;T;T

Sift4G

Benign

0.30

T;T;T;T;T;T

Polyphen

0.0070

B;B;.;B;B;.

Vest4

0.27

MutPred

0.41

Gain of catalytic residue at D62 (P = 0.0026);Gain of catalytic residue at D62 (P = 0.0026);Gain of catalytic residue at D62 (P = 0.0026);Gain of catalytic residue at D62 (P = 0.0026);Gain of catalytic residue at D62 (P = 0.0026);Gain of catalytic residue at D62 (P = 0.0026);

MVP

0.12

MPC

0.58

ClinPred

0.36

GERP RS

5.7

Varity_R

0.089

gMVP

0.29

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over