Variant chr10-1072259-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014023.4(WDR37):c.104G>A(p.Arg35Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

WDR37
NM_014023.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.53

Variant links:

Genes affected

WDR37 (HGNC:31406): (WD repeat domain 37) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. [provided by RefSeq, Jul 2008]

WDR37 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1802383).

BS2

High AC in GnomAdExome4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR37	NM_014023.4 link	c.104G>A	p.Arg35Lys	missense_variant	2/14	ENST00000263150.9	NP_054742.2	Q9Y2I8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR37	ENST00000263150.9 link	c.104G>A	p.Arg35Lys	missense_variant	2/14	1	NM_014023.4	ENSP00000263150.4		Q9Y2I8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251320

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000671

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:

0.0000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

WDR37-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 05, 2024

The WDR37 c.104G>A variant is predicted to result in the amino acid substitution p.Arg35Lys. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.54

DEOGEN2

Benign

0.035

T;.;T;.;T

Eigen

Benign

-0.033

Eigen_PC

Benign

0.12

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

.;D;D;D;D

M_CAP

Benign

0.041

MetaRNN

Benign

0.18

T;T;T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.0

M;.;.;.;M

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.13

N;.;N;.;N

REVEL

Benign

0.18

Sift

Benign

0.54

T;.;T;.;T

Sift4G

Benign

0.93

T;T;T;.;T

Polyphen

0.16

B;.;B;.;B

Vest4

0.62

MutPred

0.20

Gain of ubiquitination at R35 (P = 0.0018);Gain of ubiquitination at R35 (P = 0.0018);Gain of ubiquitination at R35 (P = 0.0018);Gain of ubiquitination at R35 (P = 0.0018);Gain of ubiquitination at R35 (P = 0.0018);

MVP

0.30

MPC

1.4

ClinPred

0.21

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.59

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