14-96382228-C-CT

Position:

• chr14-96382228-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016472.5(GSKIP):​c.-1-5dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 1,341,550 control chromosomes in the GnomAD database, including 126 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (121 hom., cov: 32)
  • Exomes 𝑓: 0.060 (5 hom.)
• Consequence: GSKIP NM_016472.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.33

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-96382228-C-CT is Benign according to our data. Variant chr14-96382228-C-CT is described in ClinVar as [Benign]. Clinvar id is 1293844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSKIP	NM_016472.5	c.-1-5dup		intron_variant		ENST00000555181.6	NP_057556.2
GSKIP	NM_001271904.1	c.-1-5dup		intron_variant			NP_001258833.1
GSKIP	NM_001271905.2	c.-1-5dup		intron_variant			NP_001258834.1
GSKIP	NM_001271906.2	c.-1-5dup		intron_variant			NP_001258835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSKIP	ENST00000555181.6	c.-1-5dup		intron_variant		1	NM_016472.5	ENSP00000450420	P1

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4120 AN: 140560 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.0539

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00332

Gnomad EAS AF: 0.00204

Gnomad SAS AF: 0.00229

Gnomad FIN AF: 0.0527

Gnomad MID AF: 0.00676

Gnomad NFE AF: 0.00989

Gnomad OTH AF: 0.0240

GnomAD4 exome AF: 0.0597 AC: 71643 AN: 1200950 Hom.: 5 Cov.: 0 AF XY: 0.0583 AC XY: 34753 AN XY: 595922

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.0416

Gnomad4 ASJ exome AF: 0.0391

Gnomad4 EAS exome AF: 0.0345

Gnomad4 SAS exome AF: 0.0530

Gnomad4 FIN exome AF: 0.0615

Gnomad4 NFE exome AF: 0.0609

Gnomad4 OTH exome AF: 0.0564

GnomAD4 genome AF: 0.0295 AC: 4146 AN: 140600 Hom.: 121 Cov.: 32 AF XY: 0.0300 AC XY: 2044 AN XY: 68026

Gnomad4 AFR AF: 0.0722

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.00332

Gnomad4 EAS AF: 0.00204

Gnomad4 SAS AF: 0.00206

Gnomad4 FIN AF: 0.0527

Gnomad4 NFE AF: 0.00990

Gnomad4 OTH AF: 0.0249

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 05, 2020

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs34610576; hg19: chr14-96848565;