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. The variant received 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

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSKIP	NM_016472.5	MANE Select	c.-1-9_-1-5delTTTTT	splice_region intron	N/A	NP_057556.2	Q9P0R6
GSKIP	NM_001271904.1		c.-1-9_-1-5delTTTTT	splice_region intron	N/A	NP_001258833.1	Q9P0R6
GSKIP	NM_001271905.2		c.-1-9_-1-5delTTTTT	splice_region intron	N/A	NP_001258834.1	Q9P0R6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSKIP	ENST00000555181.6	TSL:1 MANE Select	c.-1-18_-1-14delTTTTT	intron	N/A	ENSP00000450420.1	Q9P0R6
GSKIP	ENST00000438650.5	TSL:2	c.-1-18_-1-14delTTTTT	intron	N/A	ENSP00000412315.1	Q9P0R6
GSKIP	ENST00000554182.5	TSL:2	c.-1-18_-1-14delTTTTT	intron	N/A	ENSP00000451384.1	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

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

African (AFR)

AF:

0.0000368

AC:

AN:

27168

American (AMR)

AF:

0.00

AC:

AN:

26286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20524

East Asian (EAS)

AF:

0.00

AC:

AN:

36430

South Asian (SAS)

AF:

0.00

AC:

AN:

67976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4640

European-Non Finnish (NFE)

AF:

0.00000104

AC:

AN:

958788

Other (OTH)

AF:

0.00

AC:

AN:

51502

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over