rs145437203

chr5-111092362-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.325

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]

ACMG classification

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 GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR36	NM_139281.3	c.-95T>C		5_prime_UTR_variant	1/23	ENST00000513710.4
WDR36	XM_047416729.1	c.-95T>C		5_prime_UTR_variant	1/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR36	ENST00000513710.4	c.-95T>C		5_prime_UTR_variant	1/23	1	NM_139281.3	P1
WDR36	ENST00000505303.5	n.42T>C		non_coding_transcript_exon_variant	1/15	5
WDR36	ENST00000515784.1	n.16T>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.00752 AC: 1145 AN: 152214 Hom.: 3 Cov.: 33

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.: 15 AF XY: 0.00715 AC XY: 972 AN XY: 135900

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.: 88 Cov.: 31 AF XY: 0.00912 AC XY: 6633 AN XY: 727244

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.: 3 Cov.: 33 AF XY: 0.00728 AC XY: 542 AN XY: 74476

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.: 15

Bravo AF: 0.00859

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.0112 AC: 43

ESP6500AA AF: 0.00341 AC: 15

ESP6500EA AF: 0.0116 AC: 100

ExAC AF: 0.00654 AC: 794

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0105

EpiControl AF: 0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 29, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.61	T
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	N
MetaRNN	Benign	0.0031	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.36	T
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	T
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

Other links and lift over

dbSNP: rs145437203; hg19: chr5-110428060; COSMIC: COSV72411277; COSMIC: COSV72411277;