rs2053588

Positions:

• chr14-96379755-G-A
• chr14-96379755-G-C
• chr14-96379755-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_016472.5(GSKIP):​c.-35G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,128 control chromosomes in the GnomAD database, including 61,631 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.90 (61628 hom., cov: 31)
  • Exomes 𝑓: 1.0 (3 hom.)
• Consequence: GSKIP NM_016472.5 5_prime_UTR
• Scores: Splicing: ADA: 0.00004807
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSKIP	NM_016472.5	c.-35G>A		5_prime_UTR_variant	2/4	ENST00000555181.6
GSKIP	NM_001271904.1	c.-35G>A		5_prime_UTR_variant	2/4
GSKIP	NM_001271905.2	c.-2G>A		splice_region_variant, 5_prime_UTR_variant	2/4
GSKIP	NM_001271906.2	c.-1-2492G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSKIP	ENST00000555181.6	c.-35G>A		5_prime_UTR_variant	2/4	1	NM_016472.5	P1

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136389 AN: 152004 Hom.: 61581 Cov.: 31

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.883

GnomAD4 exome AF: 1.00 AC: 6 AN: 6 Hom.: 3 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 AMR exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.897 AC: 136493 AN: 152122 Hom.: 61628 Cov.: 31 AF XY: 0.893 AC XY: 66336 AN XY: 74322

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.860

Gnomad4 ASJ AF: 0.880

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.916

Gnomad4 OTH AF: 0.879

Alfa AF: 0.907 Hom.: 127248

Bravo AF: 0.897

Asia WGS AF: 0.714 AC: 2484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	18
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000048
SpliceAI score (max)		0.62		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.62		Position offset: 33

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

Publications

LitVar

Other links and lift over

dbSNP: rs2053588; hg19: chr14-96846092;