14-96382228-CTTTTT-CT

Variant names:

• chr14-96382228-CTTTT-C
• NM_016472.5:c.-1-8_-1-5delTTTT

Variant summary

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

The NM_016472.5(GSKIP):​c.-1-8_-1-5delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,235,614 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 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000048 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSKIP NM_016472.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSKIP	NM_016472.5	c.-1-8_-1-5delTTTT		splice_region_variant, intron_variant	Intron 2 of 3	ENST00000555181.6	NP_057556.2
GSKIP	NM_001271904.1	c.-1-8_-1-5delTTTT		splice_region_variant, intron_variant	Intron 2 of 3		NP_001258833.1
GSKIP	NM_001271905.2	c.-1-8_-1-5delTTTT		splice_region_variant, intron_variant	Intron 2 of 3		NP_001258834.1
GSKIP	NM_001271906.2	c.-1-8_-1-5delTTTT		splice_region_variant, intron_variant	Intron 1 of 2		NP_001258835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSKIP	ENST00000555181.6	c.-1-18_-1-15delTTTT		intron_variant	Intron 2 of 3	1	NM_016472.5	ENSP00000450420.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 140670 Hom.: 0 Cov.: 32 FAILED QC

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000477 AC: 59 AN: 1235614 Hom.: 0 AF XY: 0.0000604 AC XY: 37 AN XY: 612728

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000114

Gnomad4 ASJ exome AF: 0.0000975

Gnomad4 EAS exome AF: 0.0000275

Gnomad4 SAS exome AF: 0.000118

Gnomad4 FIN exome AF: 0.0000701

Gnomad4 NFE exome AF: 0.0000407

Gnomad4 OTH exome AF: 0.0000583

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 140670 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 68044

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: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-96848565;