Variant 14-63599535-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_080666.4(WDR89):c.408A>T(p.Lys136Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,613,672 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 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

WDR89
NM_080666.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.983

Variant links:

Genes affected

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

WDR89 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31985682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR89	NM_080666.4 linkuse as main transcript	c.408A>T	p.Lys136Asn	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.408A>T	p.Lys136Asn	missense_variant	3/3	6	NM_080666.4	ENSP00000480112.1	Q96FK6
WDR89	ENST00000267522.7 linkuse as main transcript	c.408A>T	p.Lys136Asn	missense_variant	3/3	1		ENSP00000267522.3	Q96FK6
WDR89	ENST00000394942.2 linkuse as main transcript	c.408A>T	p.Lys136Asn	missense_variant	2/2	5		ENSP00000378399.2	Q96FK6
WDR89	ENST00000554717.1 linkuse as main transcript	c.408A>T	p.Lys136Asn	missense_variant	4/4	2		ENSP00000451702.1	G3V4B8

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

151870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251298

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000136

AC:

199

AN:

1461802

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000162

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000145

AC:

AN:

151870

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000102

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

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

Dec 14, 2022

The c.408A>T (p.K136N) alteration is located in exon 3 (coding exon 1) of the WDR89 gene. This alteration results from a A to T substitution at nucleotide position 408, causing the lysine (K) at amino acid position 136 to be replaced by an asparagine (N). 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

Uncertain

0.49

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;T;T;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

.;D;.;D

M_CAP

Benign

0.049

MetaRNN

Benign

0.32

T;T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.7

M;M;M;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.1

N;.;N;N

REVEL

Benign

0.21

Sift

Uncertain

0.0070

D;.;D;D

Sift4G

Benign

0.17

T;T;T;.

Polyphen

1.0

D;D;D;.

Vest4

0.40

MutPred

0.48

Loss of ubiquitination at K136 (P = 0.0141);Loss of ubiquitination at K136 (P = 0.0141);Loss of ubiquitination at K136 (P = 0.0141);Loss of ubiquitination at K136 (P = 0.0141);

MVP

0.82

MPC

0.17

ClinPred

0.24

GERP RS

3.5

Varity_R

0.33

gMVP

0.43

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