3-167529119-G-C

Variant summary

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

The NM_001366157.1(WDR49):c.2339C>G(p.Thr780Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: 0.111

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=0.24003232).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR49	NM_001366157.1	c.2339C>G	p.Thr780Ser	missense_variant	14/19	ENST00000682715.1
WDR49	NM_001348951.2	c.2306C>G	p.Thr769Ser	missense_variant	14/19
WDR49	NM_001348952.2	c.2306C>G	p.Thr769Ser	missense_variant	14/19
WDR49	NM_001366158.1	c.1283C>G	p.Thr428Ser	missense_variant	11/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR49	ENST00000682715.1	c.2339C>G	p.Thr780Ser	missense_variant	14/19		NM_001366157.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2021

The c.1283C>G (p.T428S) alteration is located in exon 10 (coding exon 9) of the WDR49 gene. This alteration results from a C to G substitution at nucleotide position 1283, causing the threonine (T) at amino acid position 428 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	12
Dann	Benign	0.94
DEOGEN2	Benign	0.0037	T;.;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.58	T;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;.
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.9	N;.;.
REVEL	Benign	0.11
Sift	Uncertain	0.013	D;.;.
Sift4G	Uncertain	0.038	D;.;.
Polyphen		0.53	P;.;.
Vest4		0.27
MutPred		0.55		Gain of disorder (P = 0.0242);.;.;
MVP		0.25
MPC		0.074
ClinPred		0.51	D
GERP RS		-3.1
Varity_R		0.098
gMVP		0.074

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: chr3-167246907;