5-111106140-G-T

Variant names:

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

Variant summary

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

The NM_139281.3(WDR36):​c.1177G>T​(p.Ala393Ser) 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. 16/21 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: 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09634298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.1177G>T	p.Ala393Ser	missense_variant	Exon 11 of 23	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.1177G>T	p.Ala393Ser	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>T	p.Ala393Ser	missense_variant	Exon 11 of 23	1	NM_139281.3	ENSP00000424628.3
WDR36	ENST00000505303.5	n.1313G>T		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	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.45
DEOGEN2	Benign	0.041	T;T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.056
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.82	.;T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.096	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.91	N;N;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.98	N;.;.
REVEL	Benign	0.076
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0090	B;B;.
Vest4		0.17
MutPred		0.42		Gain of disorder (P = 0.043);Gain of disorder (P = 0.043);.;
MVP		0.32
MPC		0.028
ClinPred		0.46	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.38
gMVP		0.30

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;