Genetic Variant NM_139281.3:c.-95T>C (chr5-111092362-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_139281.3(WDR36):c.-95T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00927 in 1,614,214 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0075 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0094 ( 88 hom. )

Consequence

WDR36
NM_139281.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.325

Variant links:

Genes affected

WDR36 (HGNC:30696): (WD repeat domain 36) 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. Mutations in this gene have been associated with adult-onset primary open-angle glaucoma (POAG). [provided by RefSeq, Jul 2008]

WDR36 links:

ENSG00000253613 (HGNC:):

ENSG00000253613 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030579567).

BP6

Variant 5-111092362-T-C is Benign according to our data. Variant chr5-111092362-T-C is described in ClinVar as [Benign]. Clinvar id is 350297.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3 link	c.-95T>C		5_prime_UTR_variant	Exon 1 of 23	ENST00000513710.4	NP_644810.2	Q8NI36
WDR36	XM_047416729.1 link	c.-95T>C		5_prime_UTR_variant	Exon 1 of 21		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
WDR36	ENST00000513710 link	c.-95T>C	5_prime_UTR_variant	Exon 1 of 23	1	NM_139281.3	ENSP00000424628.3	A0A0A0MTB8
WDR36	ENST00000505303.5 link	n.42T>C	non_coding_transcript_exon_variant	Exon 1 of 15	5
WDR36	ENST00000515784.1 link	n.16T>C	non_coding_transcript_exon_variant	Exon 1 of 2	2
ENSG00000253613	ENST00000507269.3 link	n.-247A>G	upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00752

AC:

1145

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00999

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00724

AC:

1819

AN:

251336

Hom.:

AF XY:

0.00715

AC XY:

972

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00210

Gnomad AMR exome

AF:

0.00755

Gnomad ASJ exome

AF:

0.0309

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.00990

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.00945

AC:

13813

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00912

AC XY:

6633

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00881

Gnomad4 ASJ exome

AF:

0.0332

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00886

GnomAD4 genome

AF:

0.00752

AC:

1145

AN:

152332

Hom.:

Cov.:

AF XY:

0.00728

AC XY:

542

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00274

Gnomad4 AMR

AF:

0.0126

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00999

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.00859

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00341

AC:

ESP6500EA

AF:

0.0116

AC:

100

ExAC

AF:

0.00654

AC:

794

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0105

EpiControl

AF:

0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.4

DANN

Benign

0.61

DEOGEN2

Benign

0.074

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.19

.;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

0.18

N;.

REVEL

Benign

0.098

Polyphen

0.0

B;B

Vest4

0.062

MVP

0.13

MPC

0.037

ClinPred

0.0054

GERP RS

-4.7

Varity_R

0.32

gMVP

0.19

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