rs9903215

Positions:

• chr17-78993789-C-A
• chr17-78993789-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001159773.2(CANT1):​c.967G>T​(p.Ala323Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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: 0.0000014 (0 hom.)
• Consequence: CANT1 NM_001159773.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2889865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CANT1	NM_001159773.2	c.967G>T	p.Ala323Ser	missense_variant	5/5	ENST00000392446.10	NP_001153245.1
CANT1	NM_001159772.2	c.967G>T	p.Ala323Ser	missense_variant	6/6		NP_001153244.1
CANT1	NM_138793.4	c.967G>T	p.Ala323Ser	missense_variant	4/4		NP_620148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CANT1	ENST00000392446.10	c.967G>T	p.Ala323Ser	missense_variant	5/5	1	NM_001159773.2	ENSP00000376241	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248812 Hom.: 0 AF XY: 0.00000742 AC XY: 1 AN XY: 134828

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459432 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 725992

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Uncertain	0.70	D;D;D;D
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.80	T;.;.;.
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.2	L;L;L;L
MutationTaster	Benign	0.79	D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.5	.;N;N;.
REVEL	Benign	0.24
Sift	Benign	0.22	.;T;T;.
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.015	B;B;B;B
Vest4		0.17
MutPred		0.67		Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);
MVP		0.90
MPC		0.42
ClinPred		0.10	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs9903215; hg19: chr17-76989871;