17-78993643-GG-CA

Variant names:

• chr17-78993643-GG-CA
• NM_001159773.2:c.1112_1113delCCinsTG
• CANT1 p.Ala371Val

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PS1_Moderate PP3

The NM_001159773.2(CANT1):​c.1112_1113delCCinsTG​(p.Ala371Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar. Synonymous variant affecting the same amino acid position (i.e. A371A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CANT1 NM_001159773.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.45
• Publications: 0 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, ClinGen
• Desbuquois dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PS1: Transcript NM_001159773.2 (CANT1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.1112_1113delCCinsTG	p.Ala371Val	missense	N/A	NP_001153245.1	Q8WVQ1-1
	CANT1	NM_001159772.2		c.1112_1113delCCinsTG	p.Ala371Val	missense	N/A	NP_001153244.1	Q8WVQ1-1
	CANT1	NM_138793.4		c.1112_1113delCCinsTG	p.Ala371Val	missense	N/A	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.1112_1113delCCinsTG	p.Ala371Val	missense	N/A	ENSP00000376241.4	Q8WVQ1-1
	CANT1	ENST00000591773.5	TSL:1	c.1112_1113delCCinsTG	p.Ala371Val	missense	N/A	ENSP00000467437.1	Q8WVQ1-1
	CANT1	ENST00000302345.6	TSL:2	c.1112_1113delCCinsTG	p.Ala371Val	missense	N/A	ENSP00000307674.2	Q8WVQ1-1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.4

Splicing

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

hg19: chr17-76989725;