Variant 1-241683500-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_001367482.1(WDR64):c.638T>C(p.Val213Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

WDR64
NM_001367482.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

Variant links:

Genes affected

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

WDR64 links:

LOC124904603 (HGNC:):

LOC124904603 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=0.18870649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR64	NM_001367482.1 linkuse as main transcript	c.638T>C	p.Val213Ala	missense_variant	7/28	ENST00000437684.7
LOC124904603	XR_007067055.1 linkuse as main transcript	n.190-6000A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR64	ENST00000437684.7 linkuse as main transcript	c.638T>C	p.Val213Ala	missense_variant	7/28	1	NM_001367482.1	P1
WDR64	ENST00000366552.6 linkuse as main transcript	c.608T>C	p.Val203Ala	missense_variant	6/27	5			B1ANS9-1
WDR64	ENST00000461971.5 linkuse as main transcript	n.499T>C		non_coding_transcript_exon_variant	6/6	5
WDR64	ENST00000425826.3 linkuse as main transcript	c.638T>C	p.Val213Ala	missense_variant, NMD_transcript_variant	7/29	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000127

AC:

AN:

156924

Hom.:

AF XY:

0.0000241

AC XY:

AN XY:

83004

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000810

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1399392

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

690192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000560

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

Cov.:

Bravo

AF:

0.00000378

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

Oct 26, 2022

The c.608T>C (p.V203A) alteration is located in exon 6 (coding exon 6) of the WDR64 gene. This alteration results from a T to C substitution at nucleotide position 608, causing the valine (V) at amino acid position 203 to be replaced by an alanine (A). 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

0.37

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.0054

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.70

M_CAP

Benign

0.011

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.93

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.90

REVEL

Benign

0.038

Sift

Benign

0.20

Sift4G

Uncertain

0.0070

Vest4

0.46

MutPred

0.39

Loss of stability (P = 0.0149);

MVP

0.030

MPC

0.21

ClinPred

0.088

GERP RS

4.2

Varity_R

0.069

gMVP

0.50

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