Variant chr1-27303669-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001276252.2(WDTC1):c.1517C>T(p.Thr506Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,611,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

WDTC1
NM_001276252.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03226435).

BS2

High AC in GnomAd4 at 37 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDTC1	NM_001276252.2 linkuse as main transcript	c.1517C>T	p.Thr506Met	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.1517C>T	p.Thr506Met	missense_variant	14/16	1	NM_001276252.2	P5	Q8N5D0-1
WDTC1	ENST00000361771.7 linkuse as main transcript	c.1514C>T	p.Thr505Met	missense_variant	14/16	1		A1	Q8N5D0-4
WDTC1	ENST00000491239.2 linkuse as main transcript	n.1191C>T		non_coding_transcript_exon_variant	9/10	2
WDTC1	ENST00000447062.2 linkuse as main transcript	c.1517C>T	p.Thr506Met	missense_variant, NMD_transcript_variant	13/16	2			Q8N5D0-2

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000411

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000228

AC:

AN:

245722

Hom.:

AF XY:

0.000217

AC XY:

AN XY:

133606

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000332

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.000336

GnomAD4 exome

AF:

0.000228

AC:

333

AN:

1459234

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

174

AN XY:

725920

show subpopulations

Gnomad4 AFR exome

AF:

0.0000901

Gnomad4 AMR exome

AF:

0.0000452

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000699

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000271

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000243

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000263

Hom.:

Bravo

AF:

0.000162

ExAC

AF:

0.000222

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 10, 2021

The c.1514C>T (p.T505M) 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 1514, causing the threonine (T) at amino acid position 505 to be replaced by a methionine (M). 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

0.082

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.038

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

0.63

D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.46

N;N

REVEL

Benign

0.054

Sift

Benign

0.14

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.66

P;P

Vest4

0.14

MVP

0.068

MPC

1.4

ClinPred

0.039

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.068

gMVP

0.35

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