Genetic Variant NM_016472.5:c.-35G>A (chr14-96379755-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSKIP	NM_016472.5 link	c.-35G>A		5_prime_UTR_variant	Exon 2 of 4	ENST00000555181.6	NP_057556.2	Q9P0R6A0A024R6P6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSKIP	ENST00000555181.6 link	c.-35G>A		5_prime_UTR_variant	Exon 2 of 4	1	NM_016472.5	ENSP00000450420.1		Q9P0R6

Frequencies

GnomAD3 genomes

AF:

0.897

AC:

136389

AN:

152004

Hom.:

61581

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

GnomAD4 genome

AF:

0.897

AC:

136493

AN:

152122

Hom.:

61628

Cov.:

AF XY:

0.893

AC XY:

66336

AN XY:

74322

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

674

1348

2022

2696

3370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

(source)

DANN

Benign

0.43

PhyloP100

-0.96

PromoterAI

-0.044

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=298/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over