Genetic Variant GSKIP:c.-1-7_-1-5delTTT (chr14-96382228-CTTT-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_016472.5(GSKIP):c.-1-7_-1-5delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,368,910 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00086 ( 0 hom. )

Consequence

GSKIP
NM_016472.5 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.35

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 14-96382228-CTTT-C is Benign according to our data. Variant chr14-96382228-CTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3034624.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GSKIP	NM_016472.5 link	c.-1-7_-1-5delTTT	splice_region_variant, intron_variant	Intron 2 of 3	ENST00000555181.6	NP_057556.2	Q9P0R6A0A024R6P6
GSKIP	NM_001271904.1 link	c.-1-7_-1-5delTTT	splice_region_variant, intron_variant	Intron 2 of 3		NP_001258833.1	Q9P0R6A0A024R6P6
GSKIP	NM_001271905.2 link	c.-1-7_-1-5delTTT	splice_region_variant, intron_variant	Intron 2 of 3		NP_001258834.1	Q9P0R6A0A024R6P6
GSKIP	NM_001271906.2 link	c.-1-7_-1-5delTTT	splice_region_variant, intron_variant	Intron 1 of 2		NP_001258835.1	Q9P0R6A0A024R6P6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSKIP	ENST00000555181.6 link	c.-1-18_-1-16delTTT		intron_variant	Intron 2 of 3	1	NM_016472.5	ENSP00000450420.1		Q9P0R6

Frequencies

GnomAD3 genomes

AF:

0.0000142

AC:

AN:

140626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000120

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000156

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000860

AC:

1056

AN:

1228284

Hom.:

AF XY:

0.000845

AC XY:

515

AN XY:

609178

show subpopulations

Gnomad4 AFR exome

AF:

0.000925

Gnomad4 AMR exome

AF:

0.00268

Gnomad4 ASJ exome

AF:

0.00147

Gnomad4 EAS exome

AF:

0.000938

Gnomad4 SAS exome

AF:

0.00166

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.000733

Gnomad4 OTH exome

AF:

0.000860

GnomAD4 genome

AF:

0.0000142

AC:

AN:

140626

Hom.:

Cov.:

AF XY:

0.0000147

AC XY:

AN XY:

68014

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000120

Gnomad4 NFE

AF:

0.0000156

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GSKIP-related disorder

Benign:1

Dec 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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