10-48805357-T-C

Position:

• chr10-48805357-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394531.1(WDFY4):​c.4582T>C​(p.Ser1528Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,549,058 control chromosomes in the GnomAD database, including 111,682 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 0.46 (18690 hom., cov: 32)
  • Exomes 𝑓: 0.35 (92992 hom.)
• Consequence: WDFY4 NM_001394531.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

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=7.345476E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDFY4	NM_001394531.1	c.4582T>C	p.Ser1528Pro	missense_variant	26/62	ENST00000325239.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDFY4	ENST00000325239.12	c.4582T>C	p.Ser1528Pro	missense_variant	26/62	5	NM_001394531.1	P1
WDFY4	ENST00000374161.7	n.221T>C		non_coding_transcript_exon_variant	3/13	2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69503 AN: 151812 Hom.: 18643 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.457

GnomAD3 exomes AF: 0.410 AC: 63463 AN: 154822 Hom.: 14983 AF XY: 0.405 AC XY: 33232 AN XY: 81992

Gnomad AFR exome AF: 0.724

Gnomad AMR exome AF: 0.406

Gnomad ASJ exome AF: 0.351

Gnomad EAS exome AF: 0.855

Gnomad SAS exome AF: 0.434

Gnomad FIN exome AF: 0.317

Gnomad NFE exome AF: 0.314

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.345 AC: 482586 AN: 1397128 Hom.: 92992 Cov.: 49 AF XY: 0.347 AC XY: 238867 AN XY: 689182

Gnomad4 AFR exome AF: 0.731

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.869

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.458 AC: 69619 AN: 151930 Hom.: 18690 Cov.: 32 AF XY: 0.458 AC XY: 34029 AN XY: 74226

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.457

Alfa AF: 0.355 Hom.: 20486

Bravo AF: 0.478

TwinsUK AF: 0.313 AC: 1160

ALSPAC AF: 0.299 AC: 1151

ESP6500AA AF: 0.730 AC: 1011

ESP6500EA AF: 0.313 AC: 996

ExAC AF: 0.386 AC: 10450

Asia WGS AF: 0.645 AC: 2239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.9
DANN	Benign	0.90
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	7.3e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.76	N
MutationTaster	Benign	0.97	P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.045
Sift	Benign	0.31	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.023
ClinPred		0.000022	T
GERP RS		1.5
Varity_R		0.089
gMVP		0.29

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

Other links and lift over

dbSNP: rs2170132; hg19: chr10-50013402; COSMIC: COSV57424400;