Variant rs14398 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000374617.9(WDR46):c.1022T>C(p.Val341Ala) variant causes a missense change. The variant allele was found at a frequency of 0.134 in 1,613,936 control chromosomes in the GnomAD database, including 15,849 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.10 ( 995 hom., cov: 31)

Exomes 𝑓: 0.14 ( 14854 hom. )

Consequence

WDR46
ENST00000374617.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.17

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017456114).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
WDR46	NM_005452.6 linkuse as main transcript	c.1022T>C	p.Val341Ala	missense_variant	10/15	ENST00000374617.9	NP_005443.3
WDR46	NM_001164267.2 linkuse as main transcript	c.860T>C	p.Val287Ala	missense_variant	10/15		NP_001157739.1
WDR46	XM_047419523.1 linkuse as main transcript	c.1022T>C	p.Val341Ala	missense_variant	10/14		XP_047275479.1
WDR46	XM_047419524.1 linkuse as main transcript	c.1022T>C	p.Val341Ala	missense_variant	10/11		XP_047275480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
WDR46	ENST00000374617.9 linkuse as main transcript	c.1022T>C	p.Val341Ala	missense_variant	10/15	1	NM_005452.6	ENSP00000363746	P1
WDR46	ENST00000444176.1 linkuse as main transcript	c.803T>C	p.Val268Ala	missense_variant	9/10	5		ENSP00000405568
WDR46	ENST00000489905.1 linkuse as main transcript	n.218T>C		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

15243

AN:

152132

Hom.:

990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0251

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.0723

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.0781

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.135

GnomAD3 exomes

AF:

0.124

AC:

31139

AN:

250992

Hom.:

2297

AF XY:

0.132

AC XY:

17951

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.0225

Gnomad AMR exome

AF:

0.0772

Gnomad ASJ exome

AF:

0.214

Gnomad EAS exome

AF:

0.0634

Gnomad SAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.0798

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.152

GnomAD4 exome

AF:

0.137

AC:

200883

AN:

1461686

Hom.:

14854

Cov.:

AF XY:

0.140

AC XY:

101825

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0208

Gnomad4 AMR exome

AF:

0.0812

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.0622

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.0840

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.145

GnomAD4 genome

AF:

0.100

AC:

15258

AN:

152250

Hom.:

995

Cov.:

AF XY:

0.0996

AC XY:

7411

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0250

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.208

Gnomad4 EAS

AF:

0.0725

Gnomad4 SAS

AF:

0.197

Gnomad4 FIN

AF:

0.0781

Gnomad4 NFE

AF:

0.137

Gnomad4 OTH

AF:

0.139

Alfa

AF:

0.135

Hom.:

3159

Bravo

AF:

0.0979

TwinsUK

AF:

0.152

AC:

565

ALSPAC

AF:

0.144

AC:

555

ESP6500AA

AF:

0.0295

AC:

130

ESP6500EA

AF:

0.144

AC:

1237

ExAC

AF:

0.125

AC:

15178

Asia WGS

AF:

0.157

AC:

545

AN:

3478

EpiCase

AF:

0.148

EpiControl

AF:

0.146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.67

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Pathogenic

3.4

M;.

MutationTaster

Benign

1.2e-7

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.9

D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.0040

D;.

Polyphen

1.0

D;.

Vest4

0.28

MPC

1.1

ClinPred

0.028

GERP RS

4.8

Varity_R

0.46

gMVP

0.74

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over