Variant 1-241652498-A-G 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_001367482.1(WDR64):c.14A>G(p.Lys5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,552,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

WDR64
NM_001367482.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

WDR64 (HGNC:26570): (WD repeat domain 64)

WDR64 links:

OPN3 (HGNC:):

OPN3 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=0.05041969).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
WDR64	NM_001367482.1 linkuse as main transcript	c.14A>G	p.Lys5Arg	missense_variant	1/28	ENST00000437684.7	NP_001354411.1
WDR64	XM_011544087.3 linkuse as main transcript	c.14A>G	p.Lys5Arg	missense_variant	1/23		XP_011542389.1
WDR64	XM_011544091.2 linkuse as main transcript	c.14A>G	p.Lys5Arg	missense_variant	1/20		XP_011542393.1
WDR64	XM_011544092.3 linkuse as main transcript	c.14A>G	p.Lys5Arg	missense_variant	1/19		XP_011542394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR64	ENST00000437684.7 linkuse as main transcript	c.14A>G	p.Lys5Arg	missense_variant	1/28	1	NM_001367482.1	ENSP00000402446.4	A0A0C4DG52
WDR64	ENST00000366552.6 linkuse as main transcript	c.14A>G	p.Lys5Arg	missense_variant	1/27	5		ENSP00000355510.2	B1ANS9-1
WDR64	ENST00000425826.3 linkuse as main transcript	n.14A>G		non_coding_transcript_exon_variant	1/29	2		ENSP00000406342.3	H0Y6L4
OPN3	ENST00000463155.5 linkuse as main transcript	n.74+24805T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.14e-7

AC:

AN:

1399906

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690426

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0000240

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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 08, 2024

The c.14A>G (p.K5R) alteration is located in exon 1 (coding exon 1) of the WDR64 gene. This alteration results from a A to G substitution at nucleotide position 14, causing the lysine (K) at amino acid position 5 to be replaced by an arginine (R). 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

0.076

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.6

DANN

Benign

0.79

DEOGEN2

Benign

0.0032

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.46

M_CAP

Benign

0.0066

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.36

REVEL

Benign

0.020

Sift

Benign

0.44

Sift4G

Uncertain

0.047

Vest4

0.050

MutPred

0.16

Loss of methylation at K5 (P = 0.0268);

MVP

0.076

MPC

0.068

ClinPred

0.032

GERP RS

2.0

Varity_R

0.023

gMVP

0.085

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