chr10-48978370-C-T

Variant names:

• chr10-48978370-C-T
• rs2292584
• NM_001394531.1:c.9353C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394531.1(WDFY4):​c.9353C>T​(p.Pro3118Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,550,288 control chromosomes in the GnomAD database, including 188,020 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (15608 hom., cov: 32)
  • Exomes 𝑓: 0.49 (172412 hom.)
• Consequence: WDFY4 NM_001394531.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 22 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

ENSG00000233665 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=2.1889806E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394531.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	NM_001394531.1	MANE Select	c.9353C>T	p.Pro3118Leu	missense	Exon 60 of 62	NP_001381460.1	Q6ZS81-1
	WDFY4	NM_020945.2		c.9353C>T	p.Pro3118Leu	missense	Exon 60 of 62	NP_065996.1	Q6ZS81-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY4	ENST00000325239.12	TSL:5 MANE Select	c.9353C>T	p.Pro3118Leu	missense	Exon 60 of 62	ENSP00000320563.5	Q6ZS81-1
	WDFY4	ENST00000858472.1		c.9353C>T	p.Pro3118Leu	missense	Exon 60 of 62	ENSP00000528531.1
	WDFY4	ENST00000490507.1	TSL:2	c.26C>T	p.Pro9Leu	missense	Exon 1 of 3	ENSP00000491967.1	A0A1W2PQ91

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68110 AN: 151862 Hom.: 15609 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.432

GnomAD2 exomes AF: 0.451 AC: 69080 AN: 153094 AF XY: 0.456

Gnomad AFR exome AF: 0.372

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.425

Gnomad EAS exome AF: 0.322

Gnomad FIN exome AF: 0.420

Gnomad NFE exome AF: 0.512

Gnomad OTH exome AF: 0.458

GnomAD4 exome AF: 0.493 AC: 689475 AN: 1398308 Hom.: 172412 Cov.: 48 AF XY: 0.492 AC XY: 339386 AN XY: 689684

African (AFR) AF: 0.360 AC: 11366 AN: 31570

American (AMR) AF: 0.405 AC: 14409 AN: 35584

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 10750 AN: 25124

East Asian (EAS) AF: 0.253 AC: 9020 AN: 35678

South Asian (SAS) AF: 0.473 AC: 37425 AN: 79112

European-Finnish (FIN) AF: 0.427 AC: 20958 AN: 49118

Middle Eastern (MID) AF: 0.411 AC: 2339 AN: 5694

European-Non Finnish (NFE) AF: 0.515 AC: 555652 AN: 1078476

Other (OTH) AF: 0.475 AC: 27556 AN: 57952

GnomAD4 genome AF: 0.448 AC: 68132 AN: 151980 Hom.: 15608 Cov.: 32 AF XY: 0.445 AC XY: 33017 AN XY: 74268

African (AFR) AF: 0.377 AC: 15606 AN: 41432

American (AMR) AF: 0.430 AC: 6583 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1463 AN: 3472

East Asian (EAS) AF: 0.321 AC: 1653 AN: 5150

South Asian (SAS) AF: 0.477 AC: 2297 AN: 4818

European-Finnish (FIN) AF: 0.410 AC: 4333 AN: 10574

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34703 AN: 67924

Other (OTH) AF: 0.436 AC: 920 AN: 2112

Alfa AF: 0.479 Hom.: 31811

Bravo AF: 0.444

TwinsUK AF: 0.527 AC: 1954

ALSPAC AF: 0.506 AC: 1949

ESP6500AA AF: 0.376 AC: 521

ESP6500EA AF: 0.494 AC: 1572

ExAC AF: 0.392 AC: 10358

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.0
DANN	Benign	0.50
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.00022	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.13
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.088
Sift	Benign	0.35	T
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.028
ClinPred		0.0049	T
GERP RS		-1.0
PromoterAI		-0.0012	Neutral
Varity_R		0.023
gMVP		0.19
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2292584; hg19: chr10-50186415; COSMIC: COSV55428318; COSMIC: COSV55428318;