rs193920758

Variant names:

• chr4-84677403-G-A
• NM_014991.6:c.10260-7C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-84677403-G-A
• chr4-84677403-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014991.6(WDFY3):​c.10260-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,446,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: WDFY3 NM_014991.6 splice_region, intron
• Scores: Splicing: ADA: 0.00001801
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY3	NM_014991.6	c.10260-7C>T		splice_region_variant, intron_variant	Intron 66 of 67	ENST00000295888.9	NP_055806.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY3	ENST00000295888.9	c.10260-7C>T		splice_region_variant, intron_variant	Intron 66 of 67	1	NM_014991.6	ENSP00000295888.4
WDFY3	ENST00000425179.2	n.1012-7C>T		splice_region_variant, intron_variant	Intron 3 of 4	1
WDFY3	ENST00000514711.2	c.8700-7C>T		splice_region_variant, intron_variant	Intron 55 of 56	2		ENSP00000424987.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1446116 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 717870

Gnomad4 AFR exome AF: 0.0000303

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.5
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000018
dbscSNV1_RF	Benign	0.0020
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: chr4-85598556;