chr3-167500192-C-T

Variant names:

• chr3-167500192-C-T
• NM_001366157.1:c.2992G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001366157.1(WDR49):​c.2992G>A​(p.Glu998Lys) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E998Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR49 NM_001366157.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.17
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050259918).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366157.1. 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
	WDR49	NM_001366157.1	MANE Select	c.2992G>A	p.Glu998Lys	missense	Exon 18 of 19	NP_001353086.1
	WDR49	NM_001348951.2		c.2959G>A	p.Glu987Lys	missense	Exon 18 of 19	NP_001335880.1	A0A3B3IS43
	WDR49	NM_001348952.2		c.2959G>A	p.Glu987Lys	missense	Exon 18 of 19	NP_001335881.1	A0A3B3IS43

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR49	ENST00000682715.1	MANE Select	c.2992G>A	p.Glu998Lys	missense	Exon 18 of 19	ENSP00000507497.1	Q8IV35-1
	WDR49	ENST00000308378.7	TSL:1	c.1936G>A	p.Glu646Lys	missense	Exon 14 of 15	ENSP00000311343.3	Q8IV35-3
	WDR49	ENST00000647816.2		c.2959G>A	p.Glu987Lys	missense	Exon 18 of 19	ENSP00000497120.1	A0A3B3IS43

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.23
DANN	Benign	0.93
DEOGEN2	Benign	0.00084	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N
PhyloP100		-1.2
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.075
Sift	Benign	0.80	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.096
MutPred		0.23		Gain of ubiquitination at E646 (P = 0.0011)
MVP		0.38
MPC		0.031
ClinPred		0.052	T
GERP RS		3.2
Varity_R		0.031
gMVP		0.039
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr3-167217980;