3-52260423-C-G

Position:

• chr3-52260423-C-G

Variant summary

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

The NM_025222.4(WDR82):​c.505G>C​(p.Glu169Gln) variant causes a missense change involving the alteration of a 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: 33)
• Consequence: WDR82 NM_025222.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.68

Genes affected

WDR82 (HGNC:28826): (WD repeat domain 82) TMEM113 (WDR82) is a component of the mammalian SET1A (MIM 611052)/SET1B (MIM 611055) histone H3-Lys4 methyltransferase complexes (Lee and Skalnik, 2005 [PubMed 16253997]; Lee et al., 2007 [PubMed 17355966]).[supplied by OMIM, Jul 2010]

WDR82 (HGNC:):

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=0.28226143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR82	NM_025222.4	c.505G>C	p.Glu169Gln	missense_variant	5/9	ENST00000296490.8	NP_079498.2
WDR82	XM_011534136.3	c.265G>C	p.Glu89Gln	missense_variant	4/8		XP_011532438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR82	ENST00000296490.8	c.505G>C	p.Glu169Gln	missense_variant	5/9	1	NM_025222.4	ENSP00000296490.3
WDR82	ENST00000469000.5	c.163G>C	p.Glu55Gln	missense_variant	5/6	5		ENSP00000420779.2
WDR82	ENST00000487402.1	n.1366G>C		non_coding_transcript_exon_variant	3/7	2
WDR82	ENST00000463624.1	c.*22G>C		downstream_gene_variant		4		ENSP00000417313.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2024

The c.505G>C (p.E169Q) alteration is located in exon 5 (coding exon 5) of the WDR82 gene. This alteration results from a G to C substitution at nucleotide position 505, causing the glutamic acid (E) at amino acid position 169 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.21
Sift	Benign	0.35	T;T
Sift4G	Benign	0.51	T;.
Polyphen		0.0020	B;B
Vest4		0.68
MutPred		0.42		Gain of glycosylation at Y174 (P = 0.0306);.;
MVP		0.44
MPC		1.4
ClinPred		0.81	D
GERP RS		5.6
Varity_R		0.15
gMVP		0.81

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: chr3-52294439;