Variant chr10-1080436-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PM5PP5_Very_Strong

The NM_014023.4(WDR37):c.356C>T(p.Ser119Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S119Y) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WDR37
NM_014023.4 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:5

Conservation

PhyloP100: 7.76

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.

PP5

Variant 10-1080436-C-T is Pathogenic according to our data. Variant chr10-1080436-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 633617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-1080436-C-T is described in Lovd as [Pathogenic]. Variant chr10-1080436-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR37	NM_014023.4 linkuse as main transcript	c.356C>T	p.Ser119Phe	missense_variant	5/14	ENST00000263150.9	NP_054742.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR37	ENST00000263150.9 linkuse as main transcript	c.356C>T	p.Ser119Phe	missense_variant	5/14	1	NM_014023.4	ENSP00000263150	P1	Q9Y2I8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727234

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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.:

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neurooculocardiogenitourinary syndrome

Pathogenic:4

Pathogenic, criteria provided, single submitter	research	Laboratory of Medical Genetics, University of Torino	Nov 29, 2022	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Sep 23, 2024	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	Dec 20, 2022	- -
Pathogenic, criteria provided, single submitter	clinical testing	Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	Jul 18, 2022	- -

Congenital ocular coloboma;C0014544:Epilepsy;C0424605:Developmental delay;C1737329:Dysmorphism;C3714756:Intellectual disability;C5231391:Congenital cerebellar hypoplasia

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Undiagnosed Diseases Program Translational Research Laboratory, National Institutes of Health

May 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;T;.;T;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

.;D;D;D;D;D

M_CAP

Benign

0.075

MetaRNN

Uncertain

0.69

D;D;D;D;D;D

MetaSVM

Uncertain

0.16

MutationAssessor

Uncertain

2.3

M;.;.;.;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.8

D;.;D;.;D;D

REVEL

Uncertain

0.48

Sift

Benign

0.032

D;.;D;.;D;D

Sift4G

Uncertain

0.033

D;D;D;.;D;D

Polyphen

1.0

D;.;D;.;D;.

Vest4

0.66

MutPred

0.35

Loss of phosphorylation at S119 (P = 0.0277);Loss of phosphorylation at S119 (P = 0.0277);Loss of phosphorylation at S119 (P = 0.0277);Loss of phosphorylation at S119 (P = 0.0277);Loss of phosphorylation at S119 (P = 0.0277);.;

MVP

0.47

MPC

0.85

ClinPred

0.89

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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