14-96382228-CTTTTT-CTTTT

Variant names:

• chr14-96382228-CT-C
• rs34610576
• NM_016472.5:c.-1-5delT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016472.5(GSKIP):​c.-1-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 140,216 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.32 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSKIP NM_016472.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016472.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSKIP	NM_016472.5	MANE Select	c.-1-5delT		splice_region intron	N/A	NP_057556.2	Q9P0R6
	GSKIP	NM_001271904.1		c.-1-5delT		splice_region intron	N/A	NP_001258833.1	Q9P0R6
	GSKIP	NM_001271905.2		c.-1-5delT		splice_region intron	N/A	NP_001258834.1	Q9P0R6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSKIP	ENST00000555181.6	TSL:1 MANE Select	c.-1-18delT		intron	N/A	ENSP00000450420.1	Q9P0R6
	GSKIP	ENST00000438650.5	TSL:2	c.-1-18delT		intron	N/A	ENSP00000412315.1	Q9P0R6
	GSKIP	ENST00000554182.5	TSL:2	c.-1-18delT		intron	N/A	ENSP00000451384.1	Q9P0R6

Frequencies

GnomAD3 genomes AF: 0.00457 AC: 641 AN: 140182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00479

Gnomad ASJ AF: 0.00363

Gnomad EAS AF: 0.00143

Gnomad SAS AF: 0.00206

Gnomad FIN AF: 0.0222

Gnomad MID AF: 0.00340

Gnomad NFE AF: 0.00435

Gnomad OTH AF: 0.00471

GnomAD2 exomes AF: 0.390 AC: 40179 AN: 102934 AF XY: 0.396

Gnomad AFR exome AF: 0.345

Gnomad AMR exome AF: 0.396

Gnomad ASJ exome AF: 0.399

Gnomad EAS exome AF: 0.398

Gnomad FIN exome AF: 0.356

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.391

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.316 AC: 336551 AN: 1065474 Hom.: 0 Cov.: 0 AF XY: 0.317 AC XY: 167819 AN XY: 528950

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.283 AC: 6783 AN: 23996

American (AMR) AF: 0.323 AC: 7714 AN: 23878

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 6113 AN: 17856

East Asian (EAS) AF: 0.358 AC: 10863 AN: 30302

South Asian (SAS) AF: 0.317 AC: 19821 AN: 62600

European-Finnish (FIN) AF: 0.304 AC: 11545 AN: 37916

Middle Eastern (MID) AF: 0.250 AC: 1018 AN: 4072

European-Non Finnish (NFE) AF: 0.315 AC: 258351 AN: 820466

Other (OTH) AF: 0.323 AC: 14343 AN: 44388

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00460 AC: 645 AN: 140216 Hom.: 0 Cov.: 32 AF XY: 0.00540 AC XY: 366 AN XY: 67788

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00200 AC: 77 AN: 38494

American (AMR) AF: 0.00478 AC: 67 AN: 14006

Ashkenazi Jewish (ASJ) AF: 0.00363 AC: 12 AN: 3304

East Asian (EAS) AF: 0.00143 AC: 7 AN: 4884

South Asian (SAS) AF: 0.00229 AC: 10 AN: 4358

European-Finnish (FIN) AF: 0.0222 AC: 183 AN: 8252

Middle Eastern (MID) AF: 0.00741 AC: 2 AN: 270

European-Non Finnish (NFE) AF: 0.00435 AC: 278 AN: 63850

Other (OTH) AF: 0.00467 AC: 9 AN: 1926

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000316 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34610576; hg19: chr14-96848565; COSMIC: COSV68451398; COSMIC: COSV68451398;