rs6537579

Variant names:

• chr10-48826788-G-A
• rs6537579
• NM_001394531.1:c.6100G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-48826788-G-A
• chr10-48826788-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394531.1(WDFY4):​c.6100G>A​(p.Gly2034Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,551,584 control chromosomes in the GnomAD database, including 16,938 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.20 (4020 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12918 hom.)
• Consequence: WDFY4 NM_001394531.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532
• Publications: 21 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.6507845E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1	c.6100G>A	p.Gly2034Ser	missense_variant	Exon 36 of 62	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12	c.6100G>A	p.Gly2034Ser	missense_variant	Exon 36 of 62	5	NM_001394531.1	ENSP00000320563.5

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29832 AN: 151864 Hom.: 4004 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.166

GnomAD2 exomes AF: 0.145 AC: 22795 AN: 157728 AF XY: 0.142

Gnomad AFR exome AF: 0.376

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.0780

Gnomad EAS exome AF: 0.117

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.127 AC: 178042 AN: 1399602 Hom.: 12918 Cov.: 32 AF XY: 0.128 AC XY: 88109 AN XY: 690290

African (AFR) AF: 0.391 AC: 12343 AN: 31598

American (AMR) AF: 0.159 AC: 5667 AN: 35706

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 2054 AN: 25180

East Asian (EAS) AF: 0.134 AC: 4802 AN: 35738

South Asian (SAS) AF: 0.162 AC: 12828 AN: 79236

European-Finnish (FIN) AF: 0.138 AC: 6814 AN: 49380

Middle Eastern (MID) AF: 0.152 AC: 865 AN: 5700

European-Non Finnish (NFE) AF: 0.116 AC: 124782 AN: 1079004

Other (OTH) AF: 0.136 AC: 7887 AN: 58060

GnomAD4 genome AF: 0.197 AC: 29894 AN: 151982 Hom.: 4020 Cov.: 32 AF XY: 0.194 AC XY: 14384 AN XY: 74294

African (AFR) AF: 0.381 AC: 15778 AN: 41412

American (AMR) AF: 0.155 AC: 2376 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 280 AN: 3468

East Asian (EAS) AF: 0.125 AC: 646 AN: 5178

South Asian (SAS) AF: 0.157 AC: 753 AN: 4808

European-Finnish (FIN) AF: 0.137 AC: 1444 AN: 10560

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8141 AN: 67962

Other (OTH) AF: 0.166 AC: 349 AN: 2106

Alfa AF: 0.140 Hom.: 9501

Bravo AF: 0.205

TwinsUK AF: 0.126 AC: 468

ALSPAC AF: 0.113 AC: 435

ESP6500AA AF: 0.377 AC: 522

ESP6500EA AF: 0.107 AC: 342

ExAC AF: 0.154 AC: 3961

Asia WGS AF: 0.171 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.1
DANN	Benign	0.40
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.00037	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.66	N
PhyloP100		0.53
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.014
ClinPred		0.00080	T
GERP RS		-4.3
Varity_R		0.028
gMVP		0.079
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6537579; hg19: chr10-50034833; COSMIC: COSV55421224; COSMIC: COSV55421224;