5-111121055-C-T

Variant names:

• chr5-111121055-C-T
• NM_139281.3:c.2062C>T

Variant summary

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

The NM_139281.3(WDR36):​c.2062C>T​(p.Pro688Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,268 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WDR36 NM_139281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.2062C>T	p.Pro688Ser	missense_variant	Exon 19 of 23	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.2062C>T	p.Pro688Ser	missense_variant	Exon 19 of 21		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.2062C>T	p.Pro688Ser	missense_variant	Exon 19 of 23	1	NM_139281.3	ENSP00000424628.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461268 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726966

Gnomad4 AFR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.41	T;T;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	.;T;T
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Uncertain	0.31	D
MutationAssessor	Uncertain	2.2	M;M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.4	D;.;.
REVEL	Uncertain	0.43
Sift4G	Benign	0.076	T;T;T
Polyphen		0.99	D;D;.
Vest4		0.50
MutPred		0.36		Gain of phosphorylation at P744 (P = 0.0556);Gain of phosphorylation at P744 (P = 0.0556);.;
MVP		0.81
MPC		0.053
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.52
gMVP		0.42

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: chr5-110456753;