rs2170132

Positions:

• chr10-48805357-T-A
• chr10-48805357-T-C
• chr10-48805357-T-G

Variant summary

Our verdict is Likely benign. Variant got -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. 16/20 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

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 Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDFY4	NM_001394531.1	c.4582T>A	p.Ser1528Thr	missense_variant	26/62	ENST00000325239.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDFY4	ENST00000325239.12	c.4582T>A	p.Ser1528Thr	missense_variant	26/62	5	NM_001394531.1	P1
WDFY4	ENST00000374161.7	n.221T>A		non_coding_transcript_exon_variant	3/13	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.024
Sift	Benign	0.57	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.024
MutPred		0.35		Gain of helix (P = 0.132);
MVP		0.085
ClinPred		0.034	T
GERP RS		1.5
Varity_R		0.045
gMVP		0.041

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;