chr3-167522363-G-A

Variant names:

• chr3-167522363-G-A
• NM_001366157.1:c.2726C>T

Variant summary

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

The NM_001366157.1(WDR49):​c.2726C>T​(p.Thr909Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 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: -0.301

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR49	NM_001366157.1	c.2726C>T	p.Thr909Ile	missense_variant	Exon 16 of 19	ENST00000682715.1	NP_001353086.1
WDR49	NM_001348951.2	c.2693C>T	p.Thr898Ile	missense_variant	Exon 16 of 19		NP_001335880.1
WDR49	NM_001348952.2	c.2693C>T	p.Thr898Ile	missense_variant	Exon 16 of 19		NP_001335881.1
WDR49	NM_001366158.1	c.1670C>T	p.Thr557Ile	missense_variant	Exon 13 of 16		NP_001353087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR49	ENST00000682715.1	c.2726C>T	p.Thr909Ile	missense_variant	Exon 16 of 19		NM_001366157.1	ENSP00000507497.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452894 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722584

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000236

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: 0.00

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	0.086
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.4
DANN	Benign	0.97
DEOGEN2	Benign	0.0050	T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.44	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.3	N;.;.
REVEL	Benign	0.015
Sift	Benign	0.24	T;.;.
Sift4G	Benign	0.24	T;.;.
Polyphen		0.080	B;.;.
Vest4		0.11
MutPred		0.16		Gain of glycosylation at S552 (P = 0.0139);.;.;
MVP		0.18
MPC		0.030
ClinPred		0.12	T
GERP RS		1.0
Varity_R		0.049
gMVP		0.047

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.25		Position offset: -48

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: chr3-167240151;