NM_139281.3:c.542+30C>T

Variant names:

• chr5-111100751-C-T
• rs10038177
• NM_139281.3:c.542+30C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139281.3(WDR36):​c.542+30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,592,830 control chromosomes in the GnomAD database, including 191,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (23196 hom., cov: 31)
  • Exomes 𝑓: 0.48 (168680 hom.)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.149
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• glaucoma 1, open angle, G

  Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-111100751-C-T is Benign according to our data. Variant chr5-111100751-C-T is described in ClinVar as Benign. ClinVar VariationId is 1684227.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.542+30C>T		intron_variant	Intron 5 of 22	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.542+30C>T		intron_variant	Intron 5 of 20		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.542+30C>T		intron_variant	Intron 5 of 22	1	NM_139281.3	ENSP00000424628.3
WDR36	ENST00000504122.2	n.424+30C>T		intron_variant	Intron 3 of 4	4
WDR36	ENST00000505303.5	n.678+30C>T		intron_variant	Intron 5 of 14	5

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82101 AN: 151426 Hom.: 23157 Cov.: 31

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.531

GnomAD2 exomes AF: 0.527 AC: 129946 AN: 246684 AF XY: 0.526

Gnomad AFR exome AF: 0.684

Gnomad AMR exome AF: 0.639

Gnomad ASJ exome AF: 0.494

Gnomad EAS exome AF: 0.394

Gnomad FIN exome AF: 0.530

Gnomad NFE exome AF: 0.453

Gnomad OTH exome AF: 0.500

GnomAD4 exome AF: 0.476 AC: 686480 AN: 1441286 Hom.: 168680 Cov.: 27 AF XY: 0.482 AC XY: 345768 AN XY: 717484

African (AFR) AF: 0.692 AC: 22770 AN: 32926

American (AMR) AF: 0.630 AC: 27871 AN: 44212

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 12772 AN: 25808

East Asian (EAS) AF: 0.362 AC: 14197 AN: 39194

South Asian (SAS) AF: 0.682 AC: 57636 AN: 84528

European-Finnish (FIN) AF: 0.527 AC: 27788 AN: 52698

Middle Eastern (MID) AF: 0.595 AC: 3223 AN: 5414

European-Non Finnish (NFE) AF: 0.448 AC: 491022 AN: 1097002

Other (OTH) AF: 0.491 AC: 29201 AN: 59504

GnomAD4 genome AF: 0.542 AC: 82199 AN: 151544 Hom.: 23196 Cov.: 31 AF XY: 0.548 AC XY: 40577 AN XY: 74068

African (AFR) AF: 0.685 AC: 28346 AN: 41384

American (AMR) AF: 0.547 AC: 8315 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1706 AN: 3460

East Asian (EAS) AF: 0.396 AC: 2027 AN: 5124

South Asian (SAS) AF: 0.686 AC: 3305 AN: 4818

European-Finnish (FIN) AF: 0.550 AC: 5790 AN: 10518

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31076 AN: 67748

Other (OTH) AF: 0.530 AC: 1114 AN: 2102

Alfa AF: 0.485 Hom.: 24528

Bravo AF: 0.541

Asia WGS AF: 0.540 AC: 1871 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Glaucoma 1, open angle, G Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.6
DANN	Benign	0.76
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10038177; hg19: chr5-110436450; COSMIC: COSV72411563;