Variant 10-48709926-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001394531.1(WDFY4):c.194G>A(p.Arg65His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000436 in 1,399,856 control chromosomes in the GnomAD database, including 2 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R65C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000044 ( 2 hom. )

Consequence

WDFY4
NM_001394531.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.471

Variant links:

Genes affected

WDFY4 (HGNC:29323): (WDFY family member 4) Predicted to be involved in autophagy. Predicted to act upstream of or within with a positive effect on CD8-positive, alpha-beta T cell activation. Predicted to act upstream of or within antigen processing and presentation and cellular response to virus. Predicted to be located in early endosome and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

WDFY4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03880927).

BP6

Variant 10-48709926-G-A is Benign according to our data. Variant chr10-48709926-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2216068.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDFY4	NM_001394531.1 linkuse as main transcript	c.194G>A	p.Arg65His	missense_variant	2/62	ENST00000325239.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDFY4	ENST00000325239.12 linkuse as main transcript	c.194G>A	p.Arg65His	missense_variant	2/62	5	NM_001394531.1	P1	Q6ZS81-1
WDFY4	ENST00000360890.6 linkuse as main transcript	c.194G>A	p.Arg65His	missense_variant	2/11	1			Q6ZS81-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000379

AC:

AN:

158398

Hom.:

AF XY:

0.0000240

AC XY:

AN XY:

83500

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000809

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000486

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000436

AC:

AN:

1399856

Hom.:

Cov.:

AF XY:

0.0000478

AC XY:

AN XY:

690396

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.000168

Gnomad4 ASJ exome

AF:

0.0000794

Gnomad4 EAS exome

AF:

0.000112

Gnomad4 SAS exome

AF:

0.0000883

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000222

Gnomad4 OTH exome

AF:

0.0000344

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000786

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.4

DANN

Benign

0.88

DEOGEN2

Benign

0.0093

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.018

Sift

Benign

0.12

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0050

B;B

Vest4

0.034

MutPred

0.25

Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);

MVP

0.067

ClinPred

0.013

GERP RS

-2.2

Varity_R

0.025

gMVP

0.19

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over