dbSNP rs34610576: GSKIP:c.-1-9_-1-5delTTTTT (chr14-96382228-CTTTTT-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_016472.5(GSKIP):c.-1-9_-1-5delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000162 in 1,236,150 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

GSKIP
NM_016472.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GSKIP	NM_016472.5 link	c.-1-9_-1-5delTTTTT	splice_region_variant, intron_variant	Intron 2 of 3	ENST00000555181.6	NP_057556.2	Q9P0R6A0A024R6P6
GSKIP	NM_001271904.1 link	c.-1-9_-1-5delTTTTT	splice_region_variant, intron_variant	Intron 2 of 3		NP_001258833.1	Q9P0R6A0A024R6P6
GSKIP	NM_001271905.2 link	c.-1-9_-1-5delTTTTT	splice_region_variant, intron_variant	Intron 2 of 3		NP_001258834.1	Q9P0R6A0A024R6P6
GSKIP	NM_001271906.2 link	c.-1-9_-1-5delTTTTT	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_-1-14delTTTTT		intron_variant	Intron 2 of 3	1	NM_016472.5	ENSP00000450420.1		Q9P0R6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000162

AC:

AN:

1236150

Hom.:

AF XY:

0.00000163

AC XY:

AN XY:

612992

show subpopulations

Gnomad4 AFR exome

AF:

0.0000368

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000104

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over