rs6537579

Variant names:

• chr10-48826788-G-T
• rs6537579
• NM_001394531.1:c.6100G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-48826788-G-T
• chr10-48826788-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394531.1(WDFY4):​c.6100G>T​(p.Gly2034Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: WDFY4 NM_001394531.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13984457).

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.6100G>T	p.Gly2034Cys	missense	Exon 36 of 62	NP_001381460.1	Q6ZS81-1
	WDFY4	NM_020945.2		c.6100G>T	p.Gly2034Cys	missense	Exon 36 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.6100G>T	p.Gly2034Cys	missense	Exon 36 of 62	ENSP00000320563.5	Q6ZS81-1
	WDFY4	ENST00000858472.1		c.6100G>T	p.Gly2034Cys	missense	Exon 36 of 62	ENSP00000528531.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399620 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 690302

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1079018

Other (OTH) AF: 0.00 AC: 0 AN: 58060

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	8.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.41	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.53
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.14
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.017	D
Polyphen		0.65	P
Vest4		0.11
MutPred		0.51		Loss of disorder (P = 0.0576)
MVP		0.25
ClinPred		0.75	D
GERP RS		-4.3
Varity_R		0.13
gMVP		0.13
Mutation Taster		=99/1	polymorphism

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: rs6537579; hg19: chr10-50034833;