NM_001366157.1:c.2894G>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366157.1(WDR49):​c.2894G>A​(p.Arg965Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,094 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2043801).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR49	NM_001366157.1	c.2894G>A	p.Arg965Lys	missense_variant	Exon 18 of 19	ENST00000682715.1	NP_001353086.1
WDR49	NM_001348951.2	c.2861G>A	p.Arg954Lys	missense_variant	Exon 18 of 19		NP_001335880.1
WDR49	NM_001348952.2	c.2861G>A	p.Arg954Lys	missense_variant	Exon 18 of 19		NP_001335881.1
WDR49	NM_001366158.1	c.1838G>A	p.Arg613Lys	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>A	p.Arg965Lys	missense_variant	Exon 18 of 19		NM_001366157.1	ENSP00000507497.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452094 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 722246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0039	T;.;.
Eigen	Benign	-0.097
Eigen_PC	Benign	-0.038
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.48	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.97	L;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.72	N;.;.
REVEL	Benign	0.11
Sift	Benign	0.59	T;.;.
Sift4G	Benign	0.60	T;.;.
Polyphen		0.26	B;.;.
Vest4		0.32
MutPred		0.46		Gain of methylation at R613 (P = 0.021);.;.;
MVP		0.64
MPC		0.11
ClinPred		0.40	T
GERP RS		5.3
Varity_R		0.15
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-167218078;