NM_006784.3:c.128C>G

Variant names:

• chr1-117933447-C-G
• rs904180684
• NM_006784.3:c.128C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006784.3(WDR3):​c.128C>G​(p.Ala43Gly) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR3 NM_006784.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.51
• Publications: 0 publications found

Genes affected

WDR3 (HGNC:12755): (WD repeat domain 3) This gene encodes a nuclear protein containing 10 WD repeats. WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, which usually include a trp-asp at the C-terminal end. Proteins belonging to the WD repeat family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.779

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006784.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR3	NM_006784.3	MANE Select	c.128C>G	p.Ala43Gly	missense	Exon 2 of 27	NP_006775.1	Q9UNX4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR3	ENST00000349139.6	TSL:1 MANE Select	c.128C>G	p.Ala43Gly	missense	Exon 2 of 27	ENSP00000308179.4	Q9UNX4
	WDR3	ENST00000369441.7	TSL:1	c.70+58C>G		intron	N/A	ENSP00000358449.3	Q6PDA5
	WDR3	ENST00000880604.1		c.128C>G	p.Ala43Gly	missense	Exon 2 of 27	ENSP00000550663.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	0.071	D
MutationAssessor	Benign	1.9	L
PhyloP100		7.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.3	D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.025	D
Sift4G	Benign	0.099	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.78		Loss of stability (P = 0.2146)
MVP		0.92
MPC		0.54
ClinPred		0.98	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.55
gMVP		0.41
Mutation Taster		=14/86	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs904180684; hg19: chr1-118476070;