Genetic Variant GSKIP:c.-1-107T>C (chr14-96382140-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016472.5(GSKIP):c.-1-107T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0087 in 693,806 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 214 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 79 hom. )

Consequence

GSKIP
NM_016472.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.01

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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 14-96382140-T-C is Benign according to our data. Variant chr14-96382140-T-C is described in ClinVar as Benign. ClinVar VariationId is 1270285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0956 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSKIP	NM_016472.5	MANE Select	c.-1-107T>C	intron	N/A	NP_057556.2	Q9P0R6
GSKIP	NM_001271904.1		c.-1-107T>C	intron	N/A	NP_001258833.1	Q9P0R6
GSKIP	NM_001271905.2		c.-1-107T>C	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.-1-107T>C	intron	N/A	ENSP00000450420.1	Q9P0R6
GSKIP	ENST00000438650.5	TSL:2	c.-1-107T>C	intron	N/A	ENSP00000412315.1	Q9P0R6
GSKIP	ENST00000554182.5	TSL:2	c.-1-107T>C	intron	N/A	ENSP00000451384.1	Q9P0R6

Frequencies

GnomAD3 genomes

AF:

0.0283

AC:

4309

AN:

152142

Hom.:

214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0982

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0196

GnomAD4 exome

AF:

0.00319

AC:

1725

AN:

541546

Hom.:

AF XY:

0.00277

AC XY:

775

AN XY:

279334

show subpopulations

African (AFR)

AF:

0.0935

AC:

1280

AN:

13696

American (AMR)

AF:

0.00920

AC:

138

AN:

15006

Ashkenazi Jewish (ASJ)

AF:

0.00112

AC:

AN:

13360

East Asian (EAS)

AF:

0.00

AC:

AN:

30022

South Asian (SAS)

AF:

0.000131

AC:

AN:

38132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28562

Middle Eastern (MID)

AF:

0.00475

AC:

AN:

2104

European-Non Finnish (NFE)

AF:

0.000236

AC:

AN:

372432

Other (OTH)

AF:

0.00669

AC:

189

AN:

28232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

173

260

346

433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0283

AC:

4314

AN:

152260

Hom.:

214

Cov.:

AF XY:

0.0265

AC XY:

1974

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0981

AC:

4070

AN:

41500

American (AMR)

AF:

0.0122

AC:

186

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68032

Other (OTH)

AF:

0.0194

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

200

401

601

802

1002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0247

Hom.:

Bravo

AF:

0.0322

Asia WGS

AF:

0.00520

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.37

(source)

DANN

Benign

0.67

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over