Variant rs3130618 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033177.4(GPANK1):c.122G>T(p.Arg41Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,613,854 control chromosomes in the GnomAD database, including 26,676 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.17 ( 2376 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24300 hom. )

Consequence

GPANK1
NM_033177.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.47

Variant links:

Genes affected

GPANK1 (HGNC:13920): (G-patch domain and ankyrin repeats 1) This gene is located in a cluster of HLA-B-associated transcripts, which is included in the human major histocompatability complex III region. This gene encodes a protein which is thought to play a role in immunity. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2010]

GPANK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016124249).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPANK1	NM_033177.4 link	c.122G>T	p.Arg41Leu	missense_variant	2/3	ENST00000375896.9	NP_149417.1	O95872A0A024RCU2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPANK1	ENST00000375896.9 link	c.122G>T	p.Arg41Leu	missense_variant	2/3	1	NM_033177.4	ENSP00000365060.4		O95872

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25650

AN:

152040

Hom.:

2376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.0986

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.0786

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.150

GnomAD3 exomes

AF:

0.145

AC:

36482

AN:

251328

Hom.:

2998

AF XY:

0.145

AC XY:

19704

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.0764

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.0960

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.176

AC:

257446

AN:

1461696

Hom.:

24300

Cov.:

AF XY:

0.174

AC XY:

126331

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.0802

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.0466

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.169

AC:

25650

AN:

152158

Hom.:

2376

Cov.:

AF XY:

0.164

AC XY:

12214

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.0983

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.0791

Gnomad4 SAS

AF:

0.125

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.184

Gnomad4 OTH

AF:

0.149

Alfa

AF:

0.173

Hom.:

4646

Bravo

AF:

0.166

TwinsUK

AF:

0.190

AC:

706

ALSPAC

AF:

0.193

AC:

745

ESP6500AA

AF:

0.200

AC:

881

ESP6500EA

AF:

0.179

AC:

1541

ExAC

AF:

0.150

AC:

18218

Asia WGS

AF:

0.0950

AC:

331

AN:

3478

EpiCase

AF:

0.173

EpiControl

AF:

0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T;T;T;T;.;T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.69

.;.;.;.;T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.9

L;L;L;L;L;.;.;.

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-4.3

D;D;D;D;D;D;D;D

REVEL

Benign

0.14

Sift

Benign

0.057

T;T;T;T;T;T;T;T

Sift4G

Pathogenic

0.0

D;D;D;D;D;.;D;.

Polyphen

1.0

D;D;D;D;D;.;.;.

Vest4

0.25

MPC

0.95

ClinPred

0.030

GERP RS

5.2

Varity_R

0.72

gMVP

0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over