5-77437422-T-G

Position:

• chr5-77437422-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018268.4(WDR41):​c.1007A>C​(p.Gln336Pro) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 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)
• Consequence: WDR41 NM_018268.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.66

Genes affected

WDR41 (HGNC:25601): (WD repeat domain 41) Contributes to guanyl-nucleotide exchange factor activity. Involved in regulation of autophagy. Located in cytoplasm. Part of guanyl-nucleotide exchange factor complex. Colocalizes with Atg1/ULK1 kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

WDR41 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR41	NM_018268.4	c.1007A>C	p.Gln336Pro	missense_variant, splice_region_variant	11/13	ENST00000296679.9	NP_060738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR41	ENST00000296679.9	c.1007A>C	p.Gln336Pro	missense_variant, splice_region_variant	11/13	1	NM_018268.4	ENSP00000296679.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;T;.;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Uncertain	-0.095	T
MutationAssessor	Pathogenic	3.2	M;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.1	N;N;N;D
REVEL	Uncertain	0.34
Sift	Benign	0.097	T;D;D;D
Sift4G	Uncertain	0.024	D;D;D;.
Polyphen		1.0	D;.;.;.
Vest4		0.84
MutPred		0.30		Loss of stability (P = 0.1194);.;.;.;
MVP		0.73
MPC		0.30
ClinPred		0.95	D
GERP RS		6.2
Varity_R		0.42
gMVP		0.62

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: rs17856057; hg19: chr5-76733247;