3-167500290-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001366157.1(WDR49):​c.2894G>C​(p.Arg965Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,604,376 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: WDR49 NM_001366157.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.27081123).

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.2894G>C	p.Arg965Thr	missense	Exon 18 of 19	NP_001353086.1
	WDR49	NM_001348951.2		c.2861G>C	p.Arg954Thr	missense	Exon 18 of 19	NP_001335880.1	A0A3B3IS43
	WDR49	NM_001348952.2		c.2861G>C	p.Arg954Thr	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.2894G>C	p.Arg965Thr	missense	Exon 18 of 19	ENSP00000507497.1	Q8IV35-1
	WDR49	ENST00000308378.7	TSL:1	c.1838G>C	p.Arg613Thr	missense	Exon 14 of 15	ENSP00000311343.3	Q8IV35-3
	WDR49	ENST00000647816.2		c.2861G>C	p.Arg954Thr	missense	Exon 18 of 19	ENSP00000497120.1	A0A3B3IS43

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152164 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000482 AC: 7 AN: 1452094 Hom.: 0 Cov.: 32 AF XY: 0.00000277 AC XY: 2 AN XY: 722246

African (AFR) AF: 0.00 AC: 0 AN: 32690

American (AMR) AF: 0.00 AC: 0 AN: 42336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25924

East Asian (EAS) AF: 0.00 AC: 0 AN: 38982

South Asian (SAS) AF: 0.00 AC: 0 AN: 84246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108888

Other (OTH) AF: 0.000117 AC: 7 AN: 59988

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152282 Hom.: 1 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74468

African (AFR) AF: 0.00 AC: 0 AN: 41550

American (AMR) AF: 0.000915 AC: 14 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	0.13
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.0050	T
Eigen	Benign	0.019
Eigen_PC	Benign	0.057
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.97	L
PhyloP100		2.2
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.20
Sift	Benign	0.54	T
Sift4G	Benign	0.27	T
Polyphen		0.031	B
Vest4		0.54
MutPred		0.53		Loss of MoRF binding (P = 0.0398)
MVP		0.71
MPC		0.15
ClinPred		0.64	D
GERP RS		5.3
Varity_R		0.16
gMVP		0.16
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs1052017894; hg19: chr3-167218078;