rs143816093

Variant names:

• chr15-53609531-C-A
• NM_182758.4:c.2934G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-53609531-C-A
• chr15-53609531-C-G
• chr15-53609531-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_182758.4(WDR72):​c.2934G>T​(p.Trp978Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,252 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WDR72 NM_182758.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79

Genes affected

WDR72 (HGNC:26790): (WD repeat domain 72) This gene encodes a protein with eight WD-40 repeats. Mutations in this gene have been associated with amelogenesis imperfecta hypomaturation type 2A3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.917

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR72	NM_182758.4	c.2934G>T	p.Trp978Cys	missense_variant	Exon 17 of 20	ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10	c.2934G>T	p.Trp978Cys	missense_variant	Exon 17 of 20	1	NM_182758.4	ENSP00000353699.5
WDR72	ENST00000396328.5	c.2934G>T	p.Trp978Cys	missense_variant	Exon 17 of 20	1		ENSP00000379619.1
WDR72	ENST00000559418.5	c.2964G>T	p.Trp988Cys	missense_variant	Exon 16 of 19	5		ENSP00000452765.1
WDR72	ENST00000557913.5	c.2925G>T	p.Trp975Cys	missense_variant	Exon 17 of 20	5		ENSP00000453378.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461252 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726914

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.;T;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	.;D;D;D
M_CAP	Uncertain	0.099	D
MetaRNN	Pathogenic	0.92	D;D;D;D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.4	M;.;M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-10	D;D;D;D
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;.;D;.
Vest4		0.93
MutPred		0.68		Loss of catalytic residue at W978 (P = 0.0022);.;Loss of catalytic residue at W978 (P = 0.0022);.;
MVP		0.70
MPC		0.088
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.87
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.44		Position offset: -18

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: chr15-53901728;