17-78993789-C-T

Variant names:

• chr17-78993789-C-T
• rs9903215
• NM_001159773.2:c.967G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001159773.2(CANT1):​c.967G>A​(p.Ala323Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,611,790 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A323A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.010 (26 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (24 hom.)
• Consequence: CANT1 NM_001159773.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.52
• Publications: 6 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
• Desbuquois dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007646203).
• BP6: Variant 17-78993789-C-T is Benign according to our data. Variant chr17-78993789-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 325697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0101 (1538/152360) while in subpopulation AFR AF = 0.0346 (1438/41582). AF 95% confidence interval is 0.0331. There are 26 homozygotes in GnomAd4. There are 734 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CANT1	NM_001159773.2	MANE Select	c.967G>A	p.Ala323Thr	missense	Exon 5 of 5	NP_001153245.1
	CANT1	NM_001159772.2		c.967G>A	p.Ala323Thr	missense	Exon 6 of 6	NP_001153244.1
	CANT1	NM_138793.4		c.967G>A	p.Ala323Thr	missense	Exon 4 of 4	NP_620148.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CANT1	ENST00000392446.10	TSL:1 MANE Select	c.967G>A	p.Ala323Thr	missense	Exon 5 of 5	ENSP00000376241.4
	CANT1	ENST00000591773.5	TSL:1	c.967G>A	p.Ala323Thr	missense	Exon 6 of 6	ENSP00000467437.1
	CANT1	ENST00000588096.1	TSL:1	n.364G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1533 AN: 152242 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00274 AC: 682 AN: 248812 AF XY: 0.00210

Gnomad AFR exome AF: 0.0343

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00110 AC: 1599 AN: 1459430 Hom.: 24 Cov.: 31 AF XY: 0.000968 AC XY: 703 AN XY: 725990

African (AFR) AF: 0.0364 AC: 1218 AN: 33480

American (AMR) AF: 0.00259 AC: 116 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51528

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5762

European-Non Finnish (NFE) AF: 0.0000675 AC: 75 AN: 1111536

Other (OTH) AF: 0.00273 AC: 165 AN: 60364

GnomAD4 genome AF: 0.0101 AC: 1538 AN: 152360 Hom.: 26 Cov.: 33 AF XY: 0.00985 AC XY: 734 AN XY: 74506

African (AFR) AF: 0.0346 AC: 1438 AN: 41582

American (AMR) AF: 0.00444 AC: 68 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68044

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00230 Hom.: 10

Bravo AF: 0.0112

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0329 AC: 145

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00315 AC: 383

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Jun 14, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nov 28, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Desbuquois dysplasia 1 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Uncertain	0.75	D
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.78
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.0076	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.5
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.019	D
Sift4G	Benign	0.13	T
Polyphen		0.46	P
Vest4		0.30
MVP		0.94
MPC		0.46
ClinPred		0.024	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.46
Mutation Taster		=92/8	polymorphism

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: rs9903215; hg19: chr17-76989871; COSMIC: COSV56606765; COSMIC: COSV56606765;