Genetic Variant NM_001394531.1:c.9353C>T (chr10-48978370-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001394531.1(WDFY4):c.9353C>T(p.Pro3118Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,550,288 control chromosomes in the GnomAD database, including 188,020 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 15608 hom., cov: 32)

Exomes 𝑓: 0.49 ( 172412 hom. )

Consequence

WDFY4
NM_001394531.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.131

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:

ENSG00000233665 (HGNC:):

ENSG00000233665 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.1889806E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1 link	c.9353C>T	p.Pro3118Leu	missense_variant	Exon 60 of 62	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12 link	c.9353C>T	p.Pro3118Leu	missense_variant	Exon 60 of 62	5	NM_001394531.1	ENSP00000320563.5		Q6ZS81-1

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

68110

AN:

151862

Hom.:

15609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.498

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.421

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.432

GnomAD3 exomes

AF:

0.451

AC:

69080

AN:

153094

Hom.:

16033

AF XY:

0.456

AC XY:

37065

AN XY:

81236

show subpopulations

Gnomad AFR exome

AF:

0.372

Gnomad AMR exome

AF:

0.398

Gnomad ASJ exome

AF:

0.425

Gnomad EAS exome

AF:

0.322

Gnomad SAS exome

AF:

0.471

Gnomad FIN exome

AF:

0.420

Gnomad NFE exome

AF:

0.512

Gnomad OTH exome

AF:

0.458

GnomAD4 exome

AF:

0.493

AC:

689475

AN:

1398308

Hom.:

172412

Cov.:

AF XY:

0.492

AC XY:

339386

AN XY:

689684

show subpopulations

Gnomad4 AFR exome

AF:

0.360

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.428

Gnomad4 EAS exome

AF:

0.253

Gnomad4 SAS exome

AF:

0.473

Gnomad4 FIN exome

AF:

0.427

Gnomad4 NFE exome

AF:

0.515

Gnomad4 OTH exome

AF:

0.475

GnomAD4 genome

AF:

0.448

AC:

68132

AN:

151980

Hom.:

15608

Cov.:

AF XY:

0.445

AC XY:

33017

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.377

Gnomad4 AMR

AF:

0.430

Gnomad4 ASJ

AF:

0.421

Gnomad4 EAS

AF:

0.321

Gnomad4 SAS

AF:

0.477

Gnomad4 FIN

AF:

0.410

Gnomad4 NFE

AF:

0.511

Gnomad4 OTH

AF:

0.436

Alfa

AF:

0.483

Hom.:

23593

Bravo

AF:

0.444

TwinsUK

AF:

0.527

AC:

1954

ALSPAC

AF:

0.506

AC:

1949

ESP6500AA

AF:

0.376

AC:

521

ESP6500EA

AF:

0.494

AC:

1572

ExAC

AF:

0.392

AC:

10358

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.0

DANN

Benign

0.50

DEOGEN2

Benign

0.0052

T;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.18

T;T

MetaRNN

Benign

0.00022

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.088

Sift

Benign

0.35

T;.

Sift4G

Benign

0.13

T;.

Polyphen

0.0

B;.

Vest4

0.028

ClinPred

0.0049

GERP RS

-1.0

Varity_R

0.023

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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