1-241652498-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001367482.1(WDR64):ā€‹c.14A>Gā€‹(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. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 7.1e-7 ( 0 hom. )

Consequence

WDR64
NM_001367482.1 missense

Scores

1
18

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)
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]

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 UniProt
WDR64NM_001367482.1 linkc.14A>G p.Lys5Arg missense_variant 1/28 ENST00000437684.7 NP_001354411.1
WDR64XM_011544087.3 linkc.14A>G p.Lys5Arg missense_variant 1/23 XP_011542389.1
WDR64XM_011544091.2 linkc.14A>G p.Lys5Arg missense_variant 1/20 XP_011542393.1
WDR64XM_011544092.3 linkc.14A>G p.Lys5Arg missense_variant 1/19 XP_011542394.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDR64ENST00000437684.7 linkc.14A>G p.Lys5Arg missense_variant 1/281 NM_001367482.1 ENSP00000402446.4 A0A0C4DG52
WDR64ENST00000366552.6 linkc.14A>G p.Lys5Arg missense_variant 1/275 ENSP00000355510.2 B1ANS9-1
WDR64ENST00000425826.3 linkn.14A>G non_coding_transcript_exon_variant 1/292 ENSP00000406342.3 H0Y6L4
OPN3ENST00000463155.5 linkn.74+24805T>C intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
33
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:
1
AN:
1399906
Hom.:
0
Cov.:
31
AF XY:
0.00000145
AC XY:
1
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:
1
AN:
152362
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
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 submitterclinical testingAmbry GeneticsSep 08, 2024The 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
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
8.6
DANN
Benign
0.79
DEOGEN2
Benign
0.0032
T
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.090
N
LIST_S2
Benign
0.46
T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.050
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.36
N
REVEL
Benign
0.020
Sift
Benign
0.44
T
Sift4G
Uncertain
0.047
D
Vest4
0.050
MutPred
0.16
Loss of methylation at K5 (P = 0.0268);
MVP
0.076
MPC
0.068
ClinPred
0.032
T
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.

Other links and lift over

dbSNP: rs531624065; hg19: chr1-241815800; API