Genetic Variant WDR49:p.Arg965Met (chr3-167500290-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R965T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

WDR49
NM_001366157.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.20

Publications

0 publications found

Variant links:

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]

WDR49 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35925525).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR49	NM_001366157.1	MANE Select	c.2894G>T	p.Arg965Met	missense	Exon 18 of 19	NP_001353086.1
WDR49	NM_001348951.2		c.2861G>T	p.Arg954Met	missense	Exon 18 of 19	NP_001335880.1	A0A3B3IS43
WDR49	NM_001348952.2		c.2861G>T	p.Arg954Met	missense	Exon 18 of 19	NP_001335881.1	A0A3B3IS43

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR49	ENST00000682715.1	MANE Select	c.2894G>T	p.Arg965Met	missense	Exon 18 of 19	ENSP00000507497.1	Q8IV35-1
WDR49	ENST00000308378.7	TSL:1	c.1838G>T	p.Arg613Met	missense	Exon 14 of 15	ENSP00000311343.3	Q8IV35-3
WDR49	ENST00000647816.2		c.2861G>T	p.Arg954Met	missense	Exon 18 of 19	ENSP00000497120.1	A0A3B3IS43

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

240216

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.0028

Eigen

Benign

0.10

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.38

M_CAP

Benign

0.022

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.63

PhyloP100

2.2

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.5

REVEL

Benign

0.18

Sift

Benign

0.29

Sift4G

Benign

0.19

Polyphen

0.031

Vest4

0.58

MutPred

0.53

Loss of catalytic residue at R613 (P = 0.0245)

MVP

0.69

MPC

0.066

ClinPred

0.56

GERP RS

5.3

Varity_R

0.12

gMVP

0.20

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over