6-33286813-G-A

Variant names:

• chr6-33286813-G-A
• NM_005452.6:c.1097C>T

Variant summary

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

The NM_005452.6(WDR46):​c.1097C>T​(p.Ala366Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: WDR46 NM_005452.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.98

Genes affected

WDR46 (HGNC:13923): (WD repeat domain 46) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleoplasm. Predicted to be part of small-subunit processome. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

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
WDR46	NM_005452.6	c.1097C>T	p.Ala366Val	missense_variant	Exon 10 of 15	ENST00000374617.9	NP_005443.3
WDR46	NM_001164267.2	c.935C>T	p.Ala312Val	missense_variant	Exon 10 of 15		NP_001157739.1
WDR46	XM_047419523.1	c.1097C>T	p.Ala366Val	missense_variant	Exon 10 of 14		XP_047275479.1
WDR46	XM_047419524.1	c.1097C>T	p.Ala366Val	missense_variant	Exon 10 of 11		XP_047275480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR46	ENST00000374617.9	c.1097C>T	p.Ala366Val	missense_variant	Exon 10 of 15	1	NM_005452.6	ENSP00000363746.4
WDR46	ENST00000444176.1	c.878C>T	p.Ala293Val	missense_variant	Exon 9 of 10	5		ENSP00000405568.1
WDR46	ENST00000489905.1	n.293C>T		non_coding_transcript_exon_variant	Exon 3 of 6	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1097C>T (p.A366V) alteration is located in exon 10 (coding exon 10) of the WDR46 gene. This alteration results from a C to T substitution at nucleotide position 1097, causing the alanine (A) at amino acid position 366 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.016	D;.
Polyphen		0.97	D;.
Vest4		0.66
MutPred		0.62		Loss of methylation at R363 (P = 0.2219);.;
MVP		0.67
MPC		0.68
ClinPred		0.95	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr6-33254590;