rs587776898

Variant names:

• chr17-78997248-C-G
• rs587776898
• NM_001159773.2:c.375G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 5 publications found

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]

CANT1 Gene-Disease associations (from GenCC):

• Desbuquois dysplasia 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Desbuquois dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 31017.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159773.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CANT1	NM_001159773.2	MANE Select	c.375G>C	p.Trp125Cys	missense	Exon 3 of 5	NP_001153245.1
	CANT1	NM_001159772.2		c.375G>C	p.Trp125Cys	missense	Exon 4 of 6	NP_001153244.1
	CANT1	NM_138793.4		c.375G>C	p.Trp125Cys	missense	Exon 2 of 4	NP_620148.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CANT1	ENST00000392446.10	TSL:1 MANE Select	c.375G>C	p.Trp125Cys	missense	Exon 3 of 5	ENSP00000376241.4
	CANT1	ENST00000591773.5	TSL:1	c.375G>C	p.Trp125Cys	missense	Exon 4 of 6	ENSP00000467437.1
	CANT1	ENST00000302345.6	TSL:2	c.375G>C	p.Trp125Cys	missense	Exon 2 of 4	ENSP00000307674.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Desbuquois dysplasia 1 (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		7.4
MVP		0.78
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.98
Mutation Taster		=1/99	disease causing (ClinVar)

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: rs587776898; hg19: chr17-76993330;