chr14-96382228-C-CT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016472.5(GSKIP):​c.-1-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 1,341,550 control chromosomes in the GnomAD database, including 126 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (121 hom., cov: 32)
  • Exomes 𝑓: 0.060 (5 hom.)
• Consequence: GSKIP NM_016472.5 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 14-96382228-C-CT is Benign according to our data. Variant chr14-96382228-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1293844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

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.-1-5dupT		splice_region intron	N/A	NP_057556.2	Q9P0R6
	GSKIP	NM_001271904.1		c.-1-5dupT		splice_region intron	N/A	NP_001258833.1	Q9P0R6
	GSKIP	NM_001271905.2		c.-1-5dupT		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.-1-19_-1-18insT		intron	N/A	ENSP00000450420.1	Q9P0R6
	GSKIP	ENST00000438650.5	TSL:2	c.-1-19_-1-18insT		intron	N/A	ENSP00000412315.1	Q9P0R6
	GSKIP	ENST00000554182.5	TSL:2	c.-1-19_-1-18insT		intron	N/A	ENSP00000451384.1	Q9P0R6

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4120 AN: 140560 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.0539

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00332

Gnomad EAS AF: 0.00204

Gnomad SAS AF: 0.00229

Gnomad FIN AF: 0.0527

Gnomad MID AF: 0.00676

Gnomad NFE AF: 0.00989

Gnomad OTH AF: 0.0240

GnomAD2 exomes AF: 0.0544 AC: 5595 AN: 102934 AF XY: 0.0517

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.0505

Gnomad ASJ exome AF: 0.0416

Gnomad EAS exome AF: 0.0480

Gnomad FIN exome AF: 0.0837

Gnomad NFE exome AF: 0.0466

Gnomad OTH exome AF: 0.0564

GnomAD4 exome AF: 0.0597 AC: 71643 AN: 1200950 Hom.: 5 Cov.: 0 AF XY: 0.0583 AC XY: 34753 AN XY: 595922

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

African (AFR) AF: 0.106 AC: 2797 AN: 26502

American (AMR) AF: 0.0416 AC: 1083 AN: 26012

Ashkenazi Jewish (ASJ) AF: 0.0391 AC: 788 AN: 20154

East Asian (EAS) AF: 0.0345 AC: 1232 AN: 35696

South Asian (SAS) AF: 0.0530 AC: 3551 AN: 67006

European-Finnish (FIN) AF: 0.0615 AC: 2595 AN: 42198

Middle Eastern (MID) AF: 0.0422 AC: 193 AN: 4572

European-Non Finnish (NFE) AF: 0.0609 AC: 56568 AN: 928562

Other (OTH) AF: 0.0564 AC: 2836 AN: 50248

⚠️ 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: 0.0295 AC: 4146 AN: 140600 Hom.: 121 Cov.: 32 AF XY: 0.0300 AC XY: 2044 AN XY: 68026

African (AFR) AF: 0.0722 AC: 2781 AN: 38516

American (AMR) AF: 0.0117 AC: 164 AN: 14030

Ashkenazi Jewish (ASJ) AF: 0.00332 AC: 11 AN: 3312

East Asian (EAS) AF: 0.00204 AC: 10 AN: 4894

South Asian (SAS) AF: 0.00206 AC: 9 AN: 4360

European-Finnish (FIN) AF: 0.0527 AC: 440 AN: 8348

Middle Eastern (MID) AF: 0.00735 AC: 2 AN: 272

European-Non Finnish (NFE) AF: 0.00990 AC: 634 AN: 64066

Other (OTH) AF: 0.0249 AC: 48 AN: 1930

Alfa AF: 0.00291 Hom.: 1

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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;