rs6537579

Positions:

• chr10-48826788-G-A

Variant summary

Our verdict is Benign. Variant got -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. 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 0.20 (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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
WDFY4	NM_001394531.1	c.6100G>A	p.Gly2034Ser	missense_variant	36/62	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12	c.6100G>A	p.Gly2034Ser	missense_variant	36/62	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

GnomAD3 exomes AF: 0.145 AC: 22795 AN: 157728 Hom.: 1929 AF XY: 0.142 AC XY: 11865 AN XY: 83290

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 SAS exome AF: 0.164

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

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.0816

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.136

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

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.0807

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.166

Alfa AF: 0.128 Hom.: 3782

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
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

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

Other links and lift over

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