17-78993860-G-C

Variant names:

• chr17-78993860-G-C
• NM_001159773.2:c.896C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001159773.2(CANT1):​c.896C>G​(p.Pro299Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CANT1 NM_001159773.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.58

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.993

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CANT1	NM_001159773.2	c.896C>G	p.Pro299Arg	missense_variant	Exon 5 of 5	ENST00000392446.10	NP_001153245.1
CANT1	NM_001159772.2	c.896C>G	p.Pro299Arg	missense_variant	Exon 6 of 6		NP_001153244.1
CANT1	NM_138793.4	c.896C>G	p.Pro299Arg	missense_variant	Exon 4 of 4		NP_620148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CANT1	ENST00000392446.10	c.896C>G	p.Pro299Arg	missense_variant	Exon 5 of 5	1	NM_001159773.2	ENSP00000376241.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445632 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718484

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.94	D;D;D;D
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;.;.;.
M_CAP	Pathogenic	0.71	D
MetaRNN	Pathogenic	0.99	D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.9	H;H;H;H
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-8.5	.;D;D;.
REVEL	Pathogenic	0.96
Sift	Pathogenic	0.0	.;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.90
MutPred		0.92		Gain of MoRF binding (P = 0.0075);Gain of MoRF binding (P = 0.0075);Gain of MoRF binding (P = 0.0075);Gain of MoRF binding (P = 0.0075);
MVP		1.0
MPC		1.1
ClinPred		1.0	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-76989942;