10-48805357-T-A

Variant names:

• chr10-48805357-T-A
• rs2170132
• NM_001394531.1:c.4582T>A
• WDFY4 p.Ser1528Thr

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394531.1(WDFY4):​c.4582T>A​(p.Ser1528Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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: not found (cov: 32)
• Consequence: WDFY4 NM_001394531.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030231416).

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.4582T>A	p.Ser1528Thr	missense	Exon 26 of 62	NP_001381460.1	Q6ZS81-1
	WDFY4	NM_020945.2		c.4582T>A	p.Ser1528Thr	missense	Exon 26 of 62	NP_065996.1	Q6ZS81-1
	WDFY4	NM_001370153.1		c.4582T>A	p.Ser1528Thr	missense	Exon 26 of 29	NP_001357082.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.4582T>A	p.Ser1528Thr	missense	Exon 26 of 62	ENSP00000320563.5	Q6ZS81-1
	WDFY4	ENST00000858472.1		c.4582T>A	p.Ser1528Thr	missense	Exon 26 of 62	ENSP00000528531.1
	WDFY4	ENST00000374161.7	TSL:2	n.221T>A		non_coding_transcript_exon	Exon 3 of 13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.3
DANN	Benign	0.52
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.41
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.024
Sift	Benign	0.57	T
Sift4G	Benign	0.67	T
Varity_R		0.045
gMVP		0.041
Mutation Taster		=98/2	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2170132;

hg19: chr10-50013402;