chr14-96382228-CTTT-C

Position:

• chr14-96382228-CTTT-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_016472.5(GSKIP):​c.-1-7_-1-5del variant causes a splice polypyrimidine tract, 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00086 (0 hom.)
• Consequence: GSKIP NM_016472.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.35

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 Uncertain_significance. Variant got 0 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 criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSKIP	NM_016472.5	c.-1-7_-1-5del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000555181.6
GSKIP	NM_001271904.1	c.-1-7_-1-5del		splice_polypyrimidine_tract_variant, intron_variant
GSKIP	NM_001271905.2	c.-1-7_-1-5del		splice_polypyrimidine_tract_variant, intron_variant
GSKIP	NM_001271906.2	c.-1-7_-1-5del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSKIP	ENST00000555181.6	c.-1-7_-1-5del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_016472.5	P1

Frequencies

GnomAD3 genomes AF: 0.0000142 AC: 2 AN: 140626 Hom.: 0 Cov.: 32

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.: 0 AF XY: 0.000845 AC XY: 515 AN XY: 609178

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: 2 AN: 140626 Hom.: 0 Cov.: 32 AF XY: 0.0000147 AC XY: 1 AN XY: 68014

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: criteria provided, single submitter

Submissions by phenotype

GSKIP-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 16, 2019

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

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;