Variant chr5-37396380-C-T 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_018034.4(WDR70):c.302C>T(p.Thr101Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000299 in 1,603,252 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 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

WDR70
NM_018034.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

Variant links:

Genes affected

WDR70 (HGNC:25495): (WD repeat domain 70) Enables enzyme binding activity. Predicted to be involved in regulation of DNA double-strand break processing and regulation of histone H2B conserved C-terminal lysine ubiquitination. Predicted to be active in nucleus and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

WDR70 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=0.082648724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR70	NM_018034.4 link	c.302C>T	p.Thr101Met	missense_variant	5/18	ENST00000265107.9	NP_060504.1	Q9NW82
WDR70	NM_001345998.2 link	c.299C>T	p.Thr100Met	missense_variant	5/18		NP_001332927.1
WDR70	NM_001345999.2 link	c.236C>T	p.Thr79Met	missense_variant	4/17		NP_001332928.1
WDR70	XM_047417348.1 link	c.233C>T	p.Thr78Met	missense_variant	4/17		XP_047273304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR70	ENST00000265107.9 link	c.302C>T	p.Thr101Met	missense_variant	5/18	1	NM_018034.4	ENSP00000265107.4	Q9NW82
WDR70	ENST00000504564.1 link	c.302C>T	p.Thr101Met	missense_variant	5/12	1		ENSP00000425841.1	D6RIW8
WDR70	ENST00000511906.5 link	n.316C>T		non_coding_transcript_exon_variant	4/15	2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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

GnomAD3 exomes

AF:

0.0000614

AC:

AN:

244200

Hom.:

AF XY:

0.0000606

AC XY:

AN XY:

132004

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.0000308

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000138

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000449

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000269

AC:

AN:

1451096

Hom.:

Cov.:

AF XY:

0.0000250

AC XY:

AN XY:

721026

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.0000934

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000711

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000199

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000655

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

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jul 09, 2024

The c.302C>T (p.T101M) alteration is located in exon 5 (coding exon 5) of the WDR70 gene. This alteration results from a C to T substitution at nucleotide position 302, causing the threonine (T) at amino acid position 101 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

0.091

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.033

T;.

Eigen

Benign

0.062

Eigen_PC

Benign

0.096

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.66

T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.083

T;T

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

1.7

L;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.60

N;N

REVEL

Benign

0.23

Sift

Benign

0.099

T;D

Sift4G

Benign

0.086

T;T

Polyphen

0.87

P;D

Vest4

0.31

MVP

0.30

MPC

0.53

ClinPred

0.061

GERP RS

4.1

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.020

gMVP

0.17

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