Variant 1-241660637-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001367482.1(WDR64):c.253G>A(p.Asp85Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00117 in 1,551,530 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

WDR64
NM_001367482.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.41

Variant links:

Genes affected

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

WDR64 links:

LOC124904603 (HGNC:):

LOC124904603 links:

OPN3 (HGNC:14007): (opsin 3) Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. In addition to the visual opsins, mammals possess several photoreceptive non-visual opsins that are expressed in extraocular tissues. This gene, opsin 3, is strongly expressed in brain and testis and weakly expressed in liver, placenta, heart, lung, skeletal muscle, kidney, and pancreas. The gene may also be expressed in the retina. The protein has the canonical features of a photoreceptive opsin protein. [provided by RefSeq, Jul 2008]

OPN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029717296).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR64	NM_001367482.1 linkuse as main transcript	c.253G>A	p.Asp85Asn	missense_variant	2/28	ENST00000437684.7	NP_001354411.1
LOC124904603	XR_007067055.1 linkuse as main transcript	n.457C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR64	ENST00000437684.7 linkuse as main transcript	c.253G>A	p.Asp85Asn	missense_variant	2/28	1	NM_001367482.1	ENSP00000402446	P1

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

154

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000873

AC:

135

AN:

154582

Hom.:

AF XY:

0.000891

AC XY:

AN XY:

81974

show subpopulations

Gnomad AFR exome

AF:

0.000745

Gnomad AMR exome

AF:

0.00243

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:

0.00108

Gnomad OTH exome

AF:

0.00136

GnomAD4 exome

AF:

0.00119

AC:

1669

AN:

1399218

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

818

AN XY:

690134

show subpopulations

Gnomad4 AFR exome

AF:

0.000380

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000406

Gnomad4 NFE exome

AF:

0.00140

Gnomad4 OTH exome

AF:

0.00102

GnomAD4 genome

AF:

0.00101

AC:

154

AN:

152312

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00148

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.00108

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00189

AC:

ExAC

AF:

0.000439

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

Aug 02, 2021

The c.253G>A (p.D85N) alteration is located in exon 2 (coding exon 2) of the WDR64 gene. This alteration results from a G to A substitution at nucleotide position 253, causing the aspartic acid (D) at amino acid position 85 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

Benign

0.089

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.67

M_CAP

Benign

0.022

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.23

Sift

Uncertain

0.010

Sift4G

Uncertain

0.012

Vest4

0.26

MVP

0.14

MPC

0.082

ClinPred

0.068

GERP RS

2.5

Varity_R

0.094

gMVP

0.40

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