rs587776509

Variant names:

• chr17-78995118-CG-C
• rs587776509
• NM_001159773.2:c.734delC

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001159773.2(CANT1):​c.734delC​(p.Pro245ArgfsTer4) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. P245P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CANT1 NM_001159773.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.34
• Publications: 3 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), ClinGen, G2P
• Desbuquois dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-78995118-CG-C is Pathogenic according to our data. Variant chr17-78995118-CG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 278.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CANT1	NM_001159773.2	MANE Select	c.734delC	p.Pro245ArgfsTer4	frameshift	Exon 4 of 5	NP_001153245.1	Q8WVQ1-1
	CANT1	NM_001159772.2		c.734delC	p.Pro245ArgfsTer4	frameshift	Exon 5 of 6	NP_001153244.1	Q8WVQ1-1
	CANT1	NM_138793.4		c.734delC	p.Pro245ArgfsTer4	frameshift	Exon 3 of 4	NP_620148.1	Q8WVQ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CANT1	ENST00000392446.10	TSL:1 MANE Select	c.734delC	p.Pro245ArgfsTer4	frameshift	Exon 4 of 5	ENSP00000376241.4	Q8WVQ1-1
	CANT1	ENST00000591773.5	TSL:1	c.734delC	p.Pro245ArgfsTer4	frameshift	Exon 5 of 6	ENSP00000467437.1	Q8WVQ1-1
	CANT1	ENST00000588096.1	TSL:1	n.131delC		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

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
PhyloP100		9.3
Mutation Taster		=2/198	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs587776509;

hg19: chr17-76991200;