Variant 6-33287142-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005452.6(WDR46):c.964G>A(p.Val322Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00062 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00065 ( 0 hom. )

Consequence

WDR46
NM_005452.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

Variant links:

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]

WDR46 links:

WDR46 (HGNC:):

WDR46 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03643754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR46	NM_005452.6 linkuse as main transcript	c.964G>A	p.Val322Ile	missense_variant	9/15	ENST00000374617.9	NP_005443.3	O15213A8K806
WDR46	NM_001164267.2 linkuse as main transcript	c.802G>A	p.Val268Ile	missense_variant	9/15		NP_001157739.1	O15213A8K806B4DP15A0A1U9X8W1
WDR46	XM_047419523.1 linkuse as main transcript	c.964G>A	p.Val322Ile	missense_variant	9/14		XP_047275479.1
WDR46	XM_047419524.1 linkuse as main transcript	c.964G>A	p.Val322Ile	missense_variant	9/11		XP_047275480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR46	ENST00000374617.9 linkuse as main transcript	c.964G>A	p.Val322Ile	missense_variant	9/15	1	NM_005452.6	ENSP00000363746.4	O15213
WDR46	ENST00000444176.1 linkuse as main transcript	c.745G>A	p.Val249Ile	missense_variant	8/10	5		ENSP00000405568.1	H0Y6G3
WDR46	ENST00000489905.1 linkuse as main transcript	n.160G>A		non_coding_transcript_exon_variant	2/6	5

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000833

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000501

AC:

126

AN:

251458

Hom.:

AF XY:

0.000552

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000607

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000651

AC:

952

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

498

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000711

Gnomad4 OTH exome

AF:

0.000546

GnomAD4 genome

AF:

0.000316

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000834

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000516

Hom.:

Bravo

AF:

0.000434

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000527

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.000771

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.964G>A (p.V322I) alteration is located in exon 9 (coding exon 9) of the WDR46 gene. This alteration results from a G to A substitution at nucleotide position 964, causing the valine (V) at amino acid position 322 to be replaced by an isoleucine (I). 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

0.096

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.9

L;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.64

N;N

REVEL

Benign

0.18

Sift

Benign

0.069

T;T

Sift4G

Benign

0.13

T;.

Polyphen

1.0

D;.

Vest4

0.28

MVP

0.30

MPC

0.26

ClinPred

0.041

GERP RS

4.9

Varity_R

0.082

gMVP

0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over