1-117934537-A-C

Variant names:

• chr1-117934537-A-C
• NM_006784.3:c.236A>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006784.3(WDR3):​c.236A>C​(p.His79Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. H79R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WDR3 NM_006784.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.41

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR3	NM_006784.3	c.236A>C	p.His79Pro	missense_variant	Exon 3 of 27	ENST00000349139.6	NP_006775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR3	ENST00000349139.6	c.236A>C	p.His79Pro	missense_variant	Exon 3 of 27	1	NM_006784.3	ENSP00000308179.4
WDR3	ENST00000369441.7	c.*123A>C		3_prime_UTR_variant	Exon 4 of 10	1		ENSP00000358449.3
WDR3	ENST00000471680.1	n.418A>C		non_coding_transcript_exon_variant	Exon 3 of 5	5
WDR3	ENST00000487202.5	n.337A>C		non_coding_transcript_exon_variant	Exon 4 of 6	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461842 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Pathogenic	2.9	M
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.073	T
Polyphen		0.97	D
Vest4		0.84
MutPred		0.58		Loss of sheet (P = 0.1158);
MVP		0.83
MPC		0.57
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.84
gMVP		0.84

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: chr1-118477160;