rs10508908

Variant names:

• chr10-48765813-A-G
• rs10508908
• NM_001394531.1:c.2553+5373A>G

Variant summary

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

The NM_001394531.1(WDFY4):​c.2553+5373A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,974 control chromosomes in the GnomAD database, including 15,586 homozygotes. In-silico tool predicts 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 (15586 hom., cov: 32)
• Consequence: WDFY4 NM_001394531.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 9 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 (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394531.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	NM_001394531.1	MANE Select	c.2553+5373A>G		intron	N/A	NP_001381460.1	Q6ZS81-1
	WDFY4	NM_020945.2		c.2553+5373A>G		intron	N/A	NP_065996.1	Q6ZS81-1
	WDFY4	NM_001370153.1		c.2553+5373A>G		intron	N/A	NP_001357082.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.2553+5373A>G		intron	N/A	ENSP00000320563.5	Q6ZS81-1
	WDFY4	ENST00000858472.1		c.2553+5373A>G		intron	N/A	ENSP00000528531.1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68353 AN: 151856 Hom.: 15572 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.501

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.450 AC: 68405 AN: 151974 Hom.: 15586 Cov.: 32 AF XY: 0.453 AC XY: 33629 AN XY: 74262

African (AFR) AF: 0.473 AC: 19618 AN: 41442

American (AMR) AF: 0.425 AC: 6500 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1952 AN: 3470

East Asian (EAS) AF: 0.534 AC: 2749 AN: 5146

South Asian (SAS) AF: 0.459 AC: 2208 AN: 4810

European-Finnish (FIN) AF: 0.448 AC: 4723 AN: 10554

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.427 AC: 29025 AN: 67960

Other (OTH) AF: 0.496 AC: 1045 AN: 2108

Alfa AF: 0.441 Hom.: 21778

Bravo AF: 0.449

Asia WGS AF: 0.502 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.66
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10508908; hg19: chr10-49973858;