5-111092463-C-G

Variant names:

• chr5-111092463-C-G
• NM_139281.3:c.7C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139281.3(WDR36):​c.7C>G​(p.Arg3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WDR36 NM_139281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059634924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.7C>G	p.Arg3Gly	missense_variant	Exon 1 of 23	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.7C>G	p.Arg3Gly	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.7C>G	p.Arg3Gly	missense_variant	Exon 1 of 23	1	NM_139281.3	ENSP00000424628.3
WDR36	ENST00000505303.5	n.143C>G		non_coding_transcript_exon_variant	Exon 1 of 15	5
WDR36	ENST00000515784.1	n.117C>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727234

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.62
DANN	Benign	0.70
DEOGEN2	Benign	0.15	T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.32	.;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.0	N;N;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.030	N;.;.
REVEL	Benign	0.14
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.081
MutPred		0.46		Gain of catalytic residue at R59 (P = 0.0046);Gain of catalytic residue at R59 (P = 0.0046);.;
MVP		0.18
MPC		0.033
ClinPred		0.056	T
GERP RS		-5.2
Varity_R		0.11
gMVP		0.26

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: chr5-110428161;