3-52261419-C-A

Position:

• chr3-52261419-C-A

Variant summary

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

The NM_025222.4(WDR82):​c.387G>T​(p.Lys129Asn) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR82 NM_025222.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.449

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19709238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR82	NM_025222.4	c.387G>T	p.Lys129Asn	missense_variant	4/9	ENST00000296490.8	NP_079498.2
WDR82	XM_011534136.3	c.147G>T	p.Lys49Asn	missense_variant	3/8		XP_011532438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR82	ENST00000296490.8	c.387G>T	p.Lys129Asn	missense_variant	4/9	1	NM_025222.4	ENSP00000296490.3
WDR82	ENST00000469000.5	c.45G>T	p.Lys15Asn	missense_variant	4/6	5		ENSP00000420779.2
WDR82	ENST00000463624.1	c.45G>T	p.Lys15Asn	missense_variant	5/6	4		ENSP00000417313.2
WDR82	ENST00000487402.1	n.1248G>T		non_coding_transcript_exon_variant	2/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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 03, 2022

The c.387G>T (p.K129N) alteration is located in exon 4 (coding exon 4) of the WDR82 gene. This alteration results from a G to T substitution at nucleotide position 387, causing the lysine (K) at amino acid position 129 to be replaced by an asparagine (N). 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	0.80
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T;.;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.97	D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.61	N;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.092
Sift	Benign	0.29	T;T;T
Sift4G	Benign	0.29	T;.;T
Polyphen		0.0030	B;B;.
Vest4		0.63
MutPred		0.40		Loss of ubiquitination at K129 (P = 0.0224);.;.;
MVP		0.12
MPC		1.8
ClinPred		0.44	T
GERP RS		0.87
Varity_R		0.11
gMVP		0.85

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: chr3-52295435;