5-111106140-G-C

Variant names:

• chr5-111106140-G-C
• rs35703638
• NM_139281.3:c.1177G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A393T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR36 NM_139281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

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

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.1177G>C	p.Ala393Pro	missense	Exon 11 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.1177G>C	p.Ala393Pro	missense	Exon 11 of 23	ENSP00000424628.3
	WDR36	ENST00000946910.1		c.1177G>C	p.Ala393Pro	missense	Exon 11 of 23	ENSP00000616969.1
	WDR36	ENST00000856283.1		c.1174G>C	p.Ala392Pro	missense	Exon 11 of 23	ENSP00000526342.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.29
Sift4G	Uncertain	0.059	T
Polyphen		0.97	D
Vest4		0.64
MutPred		0.46		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
Mutation Taster		=69/31	polymorphism

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: rs35703638; hg19: chr5-110441839;