17-78997112-T-G

Variant names:

• chr17-78997112-T-G
• rs1014317450
• NM_001159773.2:c.511A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_001159773.2(CANT1):​c.511A>C​(p.Ile171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I171M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CANT1 NM_001159773.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.781
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr17-78997112-T-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 441248.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.18952775).

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.511A>C	p.Ile171Leu	missense	Exon 3 of 5	NP_001153245.1	Q8WVQ1-1
	CANT1	NM_001159772.2		c.511A>C	p.Ile171Leu	missense	Exon 4 of 6	NP_001153244.1	Q8WVQ1-1
	CANT1	NM_138793.4		c.511A>C	p.Ile171Leu	missense	Exon 2 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.511A>C	p.Ile171Leu	missense	Exon 3 of 5	ENSP00000376241.4	Q8WVQ1-1
	CANT1	ENST00000591773.5	TSL:1	c.511A>C	p.Ile171Leu	missense	Exon 4 of 6	ENSP00000467437.1	Q8WVQ1-1
	CANT1	ENST00000302345.6	TSL:2	c.511A>C	p.Ile171Leu	missense	Exon 2 of 4	ENSP00000307674.2	Q8WVQ1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.90
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.19	T
PhyloP100		0.78
MVP		0.48
ClinPred		0.18	T
GERP RS		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.34

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: rs1014317450; hg19: chr17-76993194;