5-111106140-G-C

Variant names:

• chr5-111106140-G-C
• NM_139281.3:c.1177G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_139281.3(WDR36):​c.1177G>C​(p.Ala393Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: WDR36 NM_139281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3234654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.1177G>C	p.Ala393Pro	missense_variant	Exon 11 of 23	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.1177G>C	p.Ala393Pro	missense_variant	Exon 11 of 21		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.1177G>C	p.Ala393Pro	missense_variant	Exon 11 of 23	1	NM_139281.3	ENSP00000424628.3
WDR36	ENST00000505303.5	n.1313G>C		non_coding_transcript_exon_variant	Exon 11 of 15	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;T;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.9	L;L;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.8	D;.;.
REVEL	Uncertain	0.29
Sift4G	Uncertain	0.059	T;T;T
Polyphen		0.97	D;D;.
Vest4		0.64
MutPred		0.46		Gain of glycosylation at A449 (P = 0.0374);Gain of glycosylation at A449 (P = 0.0374);.;
MVP		0.80
MPC		0.16
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.92
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-110441839;