NM_001366157.1:c.2894G>T

Variant names:

• chr3-167500290-C-A
• rs1052017894
• NM_001366157.1:c.2894G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001366157.1(WDR49):​c.2894G>T​(p.Arg965Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: WDR49 NM_001366157.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

Genes affected

WDR49 (HGNC:26587): (WD repeat domain 49) This gene encodes a member of the WD repeat protein family with nine WD repeats. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35925525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR49	NM_001366157.1	c.2894G>T	p.Arg965Met	missense_variant	Exon 18 of 19	ENST00000682715.1	NP_001353086.1
WDR49	NM_001348951.2	c.2861G>T	p.Arg954Met	missense_variant	Exon 18 of 19		NP_001335880.1
WDR49	NM_001348952.2	c.2861G>T	p.Arg954Met	missense_variant	Exon 18 of 19		NP_001335881.1
WDR49	NM_001366158.1	c.1838G>T	p.Arg613Met	missense_variant	Exon 15 of 16		NP_001353087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR49	ENST00000682715.1	c.2894G>T	p.Arg965Met	missense_variant	Exon 18 of 19		NM_001366157.1	ENSP00000507497.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.76
DEOGEN2	Benign	0.0028	T;.;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.38	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.63	N;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.5	N;.;.
REVEL	Benign	0.18
Sift	Benign	0.29	T;.;.
Sift4G	Benign	0.19	T;.;.
Polyphen		0.031	B;.;.
Vest4		0.58
MutPred		0.53		Loss of catalytic residue at R613 (P = 0.0245);.;.;
MVP		0.69
MPC		0.066
ClinPred		0.56	D
GERP RS		5.3
Varity_R		0.12
gMVP		0.20

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: rs1052017894; hg19: chr3-167218078;