NM_139281.3:c.111G>C

Variant names:

• chr5-111092567-G-C
• rs200337257
• NM_139281.3:c.111G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139281.3(WDR36):​c.111G>C​(p.Lys37Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 33)
• Consequence: WDR36 NM_139281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.737

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19869295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.111G>C	p.Lys37Asn	missense_variant	Exon 1 of 23	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.111G>C	p.Lys37Asn	missense_variant	Exon 1 of 21		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.111G>C	p.Lys37Asn	missense_variant	Exon 1 of 23	1	NM_139281.3	ENSP00000424628.3
WDR36	ENST00000505303.5	n.247G>C		non_coding_transcript_exon_variant	Exon 1 of 15	5
WDR36	ENST00000515784.1	n.221G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152276 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152276 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74392

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T;T;T
Eigen	Benign	-0.087
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.76	.;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.4	L;L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.77	N;.;.
REVEL	Benign	0.042
Sift4G	Benign	0.18	T;T;T
Polyphen		0.26	B;B;.
Vest4		0.27
MutPred		0.56		Loss of ubiquitination at K93 (P = 0.0446);Loss of ubiquitination at K93 (P = 0.0446);.;
MVP		0.48
MPC		0.036
ClinPred		0.79	D
GERP RS		2.9
Varity_R		0.52
gMVP		0.37

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: rs200337257; hg19: chr5-110428265;