4-84672926-T-C

Position:

• chr4-84672926-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014991.6(WDFY3):​c.10523A>G​(p.Asn3508Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDFY3 NM_014991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.62

Genes affected

WDFY3 (HGNC:20751): (WD repeat and FYVE domain containing 3) This gene encodes a phosphatidylinositol 3-phosphate-binding protein that functions as a master conductor for aggregate clearance by autophagy. This protein shuttles from the nuclear membrane to colocalize with aggregated proteins, where it complexes with other autophagic components to achieve macroautophagy-mediated clearance of these aggregated proteins. However, it is not necessary for starvation-induced macroautophagy. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13352522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDFY3	NM_014991.6	c.10523A>G	p.Asn3508Ser	missense_variant	68/68	ENST00000295888.9	NP_055806.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDFY3	ENST00000295888.9	c.10523A>G	p.Asn3508Ser	missense_variant	68/68	1	NM_014991.6	ENSP00000295888.4
WDFY3	ENST00000425179.2	n.1275A>G		non_coding_transcript_exon_variant	5/5	1
WDFY3	ENST00000514711.2	c.8963A>G	p.Asn2988Ser	missense_variant	57/57	2		ENSP00000424987.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Benign	0.80
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.18
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.63	N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.097
Sift	Benign	0.78	T
Sift4G	Benign	1.0	T
Polyphen		0.0060	B
Vest4		0.43
MutPred		0.66		Gain of catalytic residue at N3508 (P = 0.0513);
MVP		0.082
MPC		0.36
ClinPred		0.47	T
GERP RS		4.6
Varity_R		0.096
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-85594079; COSMIC: COSV55699624;