Variant 1-27303656-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_001276252.2(WDTC1):c.1504C>T(p.Arg502Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000101 in 1,606,474 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 3 hom. )

Consequence

WDTC1
NM_001276252.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79

Variant links:

Genes affected

WDTC1 (HGNC:29175): (WD and tetratricopeptide repeats 1) Predicted to enable enzyme inhibitor activity; histone binding activity; and histone deacetylase binding activity. Predicted to be involved in negative regulation of fatty acid biosynthetic process. Predicted to act upstream of or within several processes, including cellular response to insulin stimulus; glucose metabolic process; and negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of Cul4-RING E3 ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

WDTC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, WDTC1

BP4

Computational evidence support a benign effect (MetaRNN=0.21763039).

BS2

High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDTC1	NM_001276252.2 linkuse as main transcript	c.1504C>T	p.Arg502Cys	missense_variant	14/16	ENST00000319394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDTC1	ENST00000319394.8 linkuse as main transcript	c.1504C>T	p.Arg502Cys	missense_variant	14/16	1	NM_001276252.2	P5	Q8N5D0-1
WDTC1	ENST00000361771.7 linkuse as main transcript	c.1501C>T	p.Arg501Cys	missense_variant	14/16	1		A1	Q8N5D0-4
WDTC1	ENST00000491239.2 linkuse as main transcript	n.1178C>T		non_coding_transcript_exon_variant	9/10	2
WDTC1	ENST00000447062.2 linkuse as main transcript	c.1504C>T	p.Arg502Cys	missense_variant, NMD_transcript_variant	13/16	2			Q8N5D0-2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000270

AC:

AN:

241036

Hom.:

AF XY:

0.000297

AC XY:

AN XY:

131368

show subpopulations

Gnomad AFR exome

AF:

0.0000662

Gnomad AMR exome

AF:

0.000996

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000881

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000547

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000103

AC:

150

AN:

1454282

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

723510

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.000794

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000810

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000361

Gnomad4 OTH exome

AF:

0.0000832

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000534

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000247

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 30, 2021

The c.1501C>T (p.R501C) alteration is located in exon 14 (coding exon 13) of the WDTC1 gene. This alteration results from a C to T substitution at nucleotide position 1501, causing the arginine (R) at amino acid position 501 to be replaced by a cysteine (C). 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

0.20

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.047

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.059

T;T

Polyphen

0.88

P;P

Vest4

0.79

MVP

0.21

MPC

1.6

ClinPred

0.11

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.40

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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