Variant 14-63598838-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_080666.4(WDR89):c.1105G>A(p.Val369Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000623 in 1,613,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 0 hom. )

Consequence

WDR89
NM_080666.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.560

Variant links:

Genes affected

WDR89 (HGNC:20489): (WD repeat domain 89)

WDR89 links:

ENSG00000258800 (HGNC:):

ENSG00000258800 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=0.033247203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR89	NM_080666.4 linkuse as main transcript	c.1105G>A	p.Val369Met	missense_variant	3/3	ENST00000620954.2	NP_542397.1	Q96FK6A0A024R667

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR89	ENST00000620954.2 linkuse as main transcript	c.1105G>A	p.Val369Met	missense_variant	3/3	6	NM_080666.4	ENSP00000480112.1	Q96FK6
WDR89	ENST00000267522.7 linkuse as main transcript	c.1105G>A	p.Val369Met	missense_variant	3/3	1		ENSP00000267522.3	Q96FK6
WDR89	ENST00000394942.2 linkuse as main transcript	c.1105G>A	p.Val369Met	missense_variant	2/2	5		ENSP00000378399.2	Q96FK6
ENSG00000258800	ENST00000553983.1 linkuse as main transcript	n.-36C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000530

AC:

133

AN:

250888

Hom.:

AF XY:

0.000494

AC XY:

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000927

Gnomad NFE exome

AF:

0.000960

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000636

AC:

929

AN:

1461422

Hom.:

Cov.:

AF XY:

0.000647

AC XY:

470

AN XY:

726980

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000776

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000499

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.000574

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000527

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00101

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

Sep 16, 2021

The c.1105G>A (p.V369M) alteration is located in exon 3 (coding exon 1) of the WDR89 gene. This alteration results from a G to A substitution at nucleotide position 1105, causing the valine (V) at amino acid position 369 to be replaced by a methionine (M). 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

0.10

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.017

T;T;T

Eigen

Benign

-0.072

Eigen_PC

Benign

0.067

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.89

.;D;.

M_CAP

Benign

0.018

MetaRNN

Benign

0.033

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.5

L;L;L

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.35

N;.;N

REVEL

Benign

0.093

Sift

Benign

0.14

T;.;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.45

B;B;B

Vest4

0.13

MVP

0.60

MPC

0.14

ClinPred

0.021

GERP RS

4.7

Varity_R

0.078

gMVP

0.32

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