rs374993298

Variant names:

• chr1-117933381-G-A
• rs374993298
• NM_006784.3:c.62G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-117933381-G-A
• chr1-117933381-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006784.3(WDR3):​c.62G>A​(p.Ser21Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S21T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR3 NM_006784.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.40
• 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 2 ACMG points.

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

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.62G>A	p.Ser21Asn	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.62G>A	p.Ser21Asn	missense	Exon 2 of 27	ENSP00000308179.4	Q9UNX4
	WDR3	ENST00000369441.7	TSL:1	c.62G>A	p.Ser21Asn	missense	Exon 2 of 10	ENSP00000358449.3	Q6PDA5
	WDR3	ENST00000880604.1		c.62G>A	p.Ser21Asn	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

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.24
Sift	Benign	0.032	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.13	B
Vest4		0.56
MutPred		0.65		Gain of sheet (P = 0.0827)
MVP		0.69
MPC		0.11
ClinPred		0.97	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.45
Mutation Taster		=43/57	disease causing

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

Other links and lift over

dbSNP: rs374993298; hg19: chr1-118476004;