rs2053588

Variant names:

• chr14-96379755-G-A
• rs2053588
• NM_016472.5:c.-35G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001271905.2(GSKIP):​c.-2G>A variant causes a splice region 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. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.90 (61628 hom., cov: 31)
  • Exomes 𝑓: 1.0 (3 hom.)
• Consequence: GSKIP NM_001271905.2 splice_region
• Scores: Splicing: ADA: 0.00004807
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958
• Publications: 10 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 -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271905.2. 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.-35G>A		5_prime_UTR	Exon 2 of 4	NP_057556.2
	GSKIP	NM_001271905.2		c.-2G>A		splice_region	Exon 2 of 4	NP_001258834.1
	GSKIP	NM_001271904.1		c.-35G>A		5_prime_UTR	Exon 2 of 4	NP_001258833.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSKIP	ENST00000555181.6	TSL:1 MANE Select	c.-35G>A		5_prime_UTR	Exon 2 of 4	ENSP00000450420.1
	GSKIP	ENST00000554182.5	TSL:2	c.-2G>A		splice_region	Exon 2 of 4	ENSP00000451384.1
	GSKIP	ENST00000852451.1		c.-2G>A		splice_region	Exon 2 of 4	ENSP00000522510.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 1.00 AC: 2 AN: 2

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

African (AFR) AF: 0.940 AC: 39023 AN: 41514

American (AMR) AF: 0.860 AC: 13152 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3055 AN: 3472

East Asian (EAS) AF: 0.568 AC: 2923 AN: 5144

South Asian (SAS) AF: 0.820 AC: 3949 AN: 4818

European-Finnish (FIN) AF: 0.867 AC: 9144 AN: 10552

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.916 AC: 62279 AN: 68010

Other (OTH) AF: 0.879 AC: 1861 AN: 2116

Alfa AF: 0.907 Hom.: 269026

Bravo AF: 0.897

Asia WGS AF: 0.714 AC: 2484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	18
DANN	Benign	0.43
PhyloP100		-0.96
PromoterAI		-0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2053588; hg19: chr14-96846092;