NM_139281.3:c.*1427T>C

Variant names:

• chr5-111128310-T-C
• rs1043828
• NM_139281.3:c.*1427T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139281.3(WDR36):​c.*1427T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 185,036 control chromosomes in the GnomAD database, including 7,751 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (6206 hom., cov: 31)
  • Exomes 𝑓: 0.28 (1545 hom.)
• Consequence: WDR36 NM_139281.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139281.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR36	NM_139281.3	MANE Select	c.*1427T>C		3_prime_UTR	Exon 23 of 23	NP_644810.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR36	ENST00000513710.4	TSL:1 MANE Select	c.*1427T>C		3_prime_UTR	Exon 23 of 23	ENSP00000424628.3
	WDR36	ENST00000856282.1		c.*1427T>C		3_prime_UTR	Exon 23 of 23	ENSP00000526341.1
	WDR36	ENST00000929671.1		c.*1427T>C		3_prime_UTR	Exon 22 of 22	ENSP00000599730.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39978 AN: 151800 Hom.: 6206 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.0430

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.278 AC: 9196 AN: 33118 Hom.: 1545 Cov.: 0 AF XY: 0.281 AC XY: 4289 AN XY: 15256

African (AFR) AF: 0.136 AC: 164 AN: 1208

American (AMR) AF: 0.254 AC: 197 AN: 776

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 699 AN: 2072

East Asian (EAS) AF: 0.0450 AC: 288 AN: 6406

South Asian (SAS) AF: 0.0828 AC: 24 AN: 290

European-Finnish (FIN) AF: 0.438 AC: 7 AN: 16

Middle Eastern (MID) AF: 0.258 AC: 50 AN: 194

European-Non Finnish (NFE) AF: 0.354 AC: 6852 AN: 19376

Other (OTH) AF: 0.329 AC: 915 AN: 2780

GnomAD4 genome AF: 0.263 AC: 39988 AN: 151918 Hom.: 6206 Cov.: 31 AF XY: 0.255 AC XY: 18951 AN XY: 74244

African (AFR) AF: 0.134 AC: 5563 AN: 41494

American (AMR) AF: 0.288 AC: 4381 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1245 AN: 3472

East Asian (EAS) AF: 0.0429 AC: 222 AN: 5174

South Asian (SAS) AF: 0.104 AC: 503 AN: 4818

European-Finnish (FIN) AF: 0.294 AC: 3101 AN: 10530

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23867 AN: 67884

Other (OTH) AF: 0.286 AC: 603 AN: 2110

Alfa AF: 0.321 Hom.: 23790

Bravo AF: 0.264

Asia WGS AF: 0.112 AC: 388 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.74
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1043828; hg19: chr5-110464008;