Variant rs116074753 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001103146.3(GIGYF2):c.1370A>C(p.Asn457Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 1,613,646 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 1 hom. )

Consequence

GIGYF2
NM_001103146.3 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: -0.758

Variant links:

Genes affected

GIGYF2 (HGNC:11960): (GRB10 interacting GYF protein 2) This gene contains CAG trinucleotide repeats and encodes a protein containing several stretches of polyglutamine residues. The encoded protein may be involved in the regulation of tyrosine kinase receptor signaling. This gene is located in a chromosomal region that was genetically linked to Parkinson disease type 11, and mutations in this gene were thought to be causative for this disease. However, more recent studies in different populations have been unable to replicate this association. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

GIGYF2 links:

GIGYF2 (HGNC:):

GIGYF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06393552).

BS2

High AC in GnomAd4 at 53 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 linkuse as main transcript	c.1370A>C	p.Asn457Thr	missense_variant	13/29	ENST00000373563.9	NP_001096616.1	Q6Y7W6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIGYF2	ENST00000373563.9 linkuse as main transcript	c.1370A>C	p.Asn457Thr	missense_variant	13/29	1	NM_001103146.3	ENSP00000362664.5		Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.000349

AC:

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000618

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000394

AC:

AN:

251254

Hom.:

AF XY:

0.000390

AC XY:

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000757

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000478

AC:

698

AN:

1461608

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

333

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000584

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000349

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000618

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000631

Hom.:

Bravo

AF:

0.000344

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000387

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.00101

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Parkinson disease 11, autosomal dominant, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Aug 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.7

DANN

Benign

0.87

DEOGEN2

Benign

0.10

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.72

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

M_CAP

Benign

0.018

MetaRNN

Benign

0.064

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

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.41

.;N;N;N;N;N;N;N

REVEL

Benign

0.026

Sift

Benign

0.32

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

Sift4G

Benign

0.41

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

Polyphen

0.0

.;B;.;B;.;.;.;.

Vest4

0.13

MVP

0.26

MPC

0.33

ClinPred

0.012

GERP RS

-3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.022

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over