4-84797795-A-T

Position:

• chr4-84797795-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014991.6(WDFY3):​c.2935+201T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,184 control chromosomes in the GnomAD database, including 15,675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (15675 hom., cov: 30)
• Consequence: WDFY3 NM_014991.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.28

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]

WDFY3-AS1 (HGNC:40935): (WDFY3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 4-84797795-A-T is Benign according to our data. Variant chr4-84797795-A-T is described in ClinVar as [Benign]. Clinvar id is 1226658.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDFY3	NM_014991.6	c.2935+201T>A		intron_variant		ENST00000295888.9	NP_055806.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDFY3	ENST00000295888.9	c.2935+201T>A		intron_variant		1	NM_014991.6	ENSP00000295888.4
WDFY3	ENST00000514711.2	c.1471+201T>A		intron_variant		2		ENSP00000424987.2
WDFY3-AS1	ENST00000510449.2	n.141+1041A>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67512 AN: 151064 Hom.: 15637 Cov.: 30

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.447 AC: 67603 AN: 151184 Hom.: 15675 Cov.: 30 AF XY: 0.441 AC XY: 32582 AN XY: 73818

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.506

Alfa AF: 0.405 Hom.: 1538

Bravo AF: 0.468

Asia WGS AF: 0.440 AC: 1529 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.22

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: rs2170935; hg19: chr4-85718948;