rs587776898

Positions:

• chr17-78997248-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_001159773.2(CANT1):​c.375G>C​(p.Trp125Cys) 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CANT1 NM_001159773.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.42

Genes affected

CANT1 (HGNC:19721): (calcium activated nucleotidase 1) This protein encoded by this gene belongs to the apyrase family. It functions as a calcium-dependent nucleotidase with a preference for UDP. Mutations in this gene are associated with Desbuquois dysplasia with hand anomalies. Alternatively spliced transcript variants have been noted for this gene.[provided by RefSeq, Mar 2010]

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, 0.828
• PP5: Variant 17-78997248-C-G is Pathogenic according to our data. Variant chr17-78997248-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 31017.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CANT1	NM_001159773.2	c.375G>C	p.Trp125Cys	missense_variant	3/5	ENST00000392446.10	NP_001153245.1
CANT1	NM_001159772.2	c.375G>C	p.Trp125Cys	missense_variant	4/6		NP_001153244.1
CANT1	NM_138793.4	c.375G>C	p.Trp125Cys	missense_variant	2/4		NP_620148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CANT1	ENST00000392446.10	c.375G>C	p.Trp125Cys	missense_variant	3/5	1	NM_001159773.2	ENSP00000376241	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Desbuquois dysplasia 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.26	T
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.83	D
MutationTaster	Benign	1.0	D;D;D
MVP		0.78
ClinPred		1.0	D
GERP RS		5.3

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

LitVar

Other links and lift over

dbSNP: rs587776898; hg19: chr17-76993330;