rs17009220

chr4-84717462-G-C

Variant summary

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

The NM_014991.6(WDFY3):c.7755-446C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.045 in 152,262 control chromosomes in the GnomAD database, including 284 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 0.045 (284 hom., cov: 31)
• Consequence: WDFY3 NM_014991.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDFY3	NM_014991.6	c.7755-446C>G		intron_variant		ENST00000295888.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDFY3	ENST00000295888.9	c.7755-446C>G		intron_variant		1	NM_014991.6	P1
WDFY3	ENST00000514711.2	c.6195-446C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 6846 AN: 152144 Hom.: 282 Cov.: 31

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0526

Gnomad OTH AF: 0.0340

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

GnomAD4 genome AF: 0.0450 AC: 6858 AN: 152262 Hom.: 284 Cov.: 31 AF XY: 0.0459 AC XY: 3414 AN XY: 74448

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.0526

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0469 Hom.: 45

Bravo AF: 0.0505

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.5
Dann	Benign	0.28

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: rs17009220; hg19: chr4-85638615;