Variant 14-96363661-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016472.5(GSKIP):c.-103+93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,898 control chromosomes in the GnomAD database, including 9,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9193 hom., cov: 32)

Exomes 𝑓: 0.35 ( 14 hom. )

Consequence

GSKIP
NM_016472.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.15

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 14-96363661-G-A is Benign according to our data. Variant chr14-96363661-G-A is described in ClinVar as [Benign]. Clinvar id is 1278620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
GSKIP	NM_016472.5 linkuse as main transcript	c.-103+93G>A	intron_variant	ENST00000555181.6	NP_057556.2
GSKIP	NM_001271905.2 linkuse as main transcript	c.-70+93G>A	intron_variant		NP_001258834.1
GSKIP	NM_001271906.2 linkuse as main transcript	c.-2+93G>A	intron_variant		NP_001258835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSKIP	ENST00000555181.6 linkuse as main transcript	c.-103+93G>A		intron_variant		1	NM_016472.5	ENSP00000450420	P1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49426

AN:

151598

Hom.:

9195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.315

GnomAD4 exome

AF:

0.345

AC:

AN:

194

Hom.:

Cov.:

AF XY:

0.342

AC XY:

AN XY:

146

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.380

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

0.326

AC:

49432

AN:

151704

Hom.:

9193

Cov.:

AF XY:

0.321

AC XY:

23833

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.235

Gnomad4 FIN

AF:

0.347

Gnomad4 NFE

AF:

0.425

Gnomad4 OTH

AF:

0.312

Alfa

AF:

0.364

Hom.:

1335

Bravo

AF:

0.325

Asia WGS

AF:

0.198

AC:

685

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 01, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.1

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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