Variant 14-63599597-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080666.4(WDR89):c.346A>G(p.Asn116Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,796 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WDR89
NM_080666.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09477055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR89	NM_080666.4 linkuse as main transcript	c.346A>G	p.Asn116Asp	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.346A>G	p.Asn116Asp	missense_variant	3/3	6	NM_080666.4	ENSP00000480112.1	Q96FK6
WDR89	ENST00000267522.7 linkuse as main transcript	c.346A>G	p.Asn116Asp	missense_variant	3/3	1		ENSP00000267522.3	Q96FK6
WDR89	ENST00000394942.2 linkuse as main transcript	c.346A>G	p.Asn116Asp	missense_variant	2/2	5		ENSP00000378399.2	Q96FK6
WDR89	ENST00000554717.1 linkuse as main transcript	c.346A>G	p.Asn116Asp	missense_variant	4/4	2		ENSP00000451702.1	G3V4B8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152198

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

250986

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461796

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000412

AC:

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

May 09, 2023

The c.346A>G (p.N116D) alteration is located in exon 3 (coding exon 1) of the WDR89 gene. This alteration results from a A to G substitution at nucleotide position 346, causing the asparagine (N) at amino acid position 116 to be replaced by an aspartic acid (D). 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

0.27

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;T;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.0046

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

.;T;.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.095

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.2

M;M;M;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.87

N;.;N;N

REVEL

Benign

0.050

Sift

Benign

0.17

T;.;T;T

Sift4G

Benign

0.35

T;T;T;.

Polyphen

0.083

B;B;B;.

Vest4

0.41

MutPred

0.60

Gain of ubiquitination at K111 (P = 0.0685);Gain of ubiquitination at K111 (P = 0.0685);Gain of ubiquitination at K111 (P = 0.0685);Gain of ubiquitination at K111 (P = 0.0685);

MVP

0.63

MPC

0.13

ClinPred

0.072

GERP RS

4.5

Varity_R

0.10

gMVP

0.39

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