NM_001394531.1:c.591+3G>A

Variant names:

• chr10-48723570-G-A
• rs111563360
• NM_001394531.1:c.591+3G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001394531.1(WDFY4):​c.591+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00438 in 1,551,792 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (123 hom., cov: 31)
  • Exomes 𝑓: 0.0024 (113 hom.)
• Consequence: WDFY4 NM_001394531.1 splice_region, intron
• Scores: Splicing: ADA: 0.001357
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.45
• Publications: 1 publications found

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]

WDFY4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 10-48723570-G-A is Benign according to our data. Variant chr10-48723570-G-A is described in ClinVar as [Benign]. Clinvar id is 785317.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDFY4	NM_001394531.1	c.591+3G>A		splice_region_variant, intron_variant	Intron 5 of 61	ENST00000325239.12	NP_001381460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDFY4	ENST00000325239.12	c.591+3G>A		splice_region_variant, intron_variant	Intron 5 of 61	5	NM_001394531.1	ENSP00000320563.5
WDFY4	ENST00000360890.6	c.591+3G>A		splice_region_variant, intron_variant	Intron 5 of 10	1		ENSP00000354141.2

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3385 AN: 152140 Hom.: 123 Cov.: 31

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00527 AC: 831 AN: 157656 AF XY: 0.00418

Gnomad AFR exome AF: 0.0798

Gnomad AMR exome AF: 0.00523

Gnomad ASJ exome AF: 0.000823

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000343

Gnomad OTH exome AF: 0.00471

GnomAD4 exome AF: 0.00244 AC: 3413 AN: 1399534 Hom.: 113 Cov.: 31 AF XY: 0.00217 AC XY: 1498 AN XY: 690260

African (AFR) AF: 0.0814 AC: 2572 AN: 31588

American (AMR) AF: 0.00588 AC: 210 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.000437 AC: 11 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.000278 AC: 22 AN: 79216

European-Finnish (FIN) AF: 0.0000202 AC: 1 AN: 49436

Middle Eastern (MID) AF: 0.00534 AC: 30 AN: 5618

European-Non Finnish (NFE) AF: 0.000228 AC: 246 AN: 1078992

Other (OTH) AF: 0.00553 AC: 321 AN: 58068

GnomAD4 genome AF: 0.0223 AC: 3391 AN: 152258 Hom.: 123 Cov.: 31 AF XY: 0.0218 AC XY: 1623 AN XY: 74436

African (AFR) AF: 0.0755 AC: 3138 AN: 41536

American (AMR) AF: 0.0110 AC: 168 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4818

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68020

Other (OTH) AF: 0.0194 AC: 41 AN: 2112

Alfa AF: 0.0150 Hom.: 36

Bravo AF: 0.0258

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Benign	0.94
PhyloP100		1.5
Mutation Taster		=75/25	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0014
dbscSNV1_RF	Benign	0.016
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

Other links and lift over

dbSNP: rs111563360; hg19: chr10-49931615;