17-78991756-A-C

Variant names:

• chr17-78991756-A-C
• rs192546263
• NM_001159773.2:c.*1794T>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001159773.2(CANT1):​c.*1794T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 216,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: CANT1 NM_001159773.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.173
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 17-78991756-A-C is Benign according to our data. Variant chr17-78991756-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 325665.Status of the report is criteria_provided_single_submitter, 1 stars.

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.*1794T>G		3_prime_UTR	Exon 5 of 5	NP_001153245.1	Q8WVQ1-1
	CANT1	NM_001159772.2		c.*1794T>G		3_prime_UTR	Exon 6 of 6	NP_001153244.1	Q8WVQ1-1
	CANT1	NM_138793.4		c.*1794T>G		3_prime_UTR	Exon 4 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.*1794T>G		3_prime_UTR	Exon 5 of 5	ENSP00000376241.4	Q8WVQ1-1
	CANT1	ENST00000302345.6	TSL:2	c.*1794T>G		3_prime_UTR	Exon 4 of 4	ENSP00000307674.2	Q8WVQ1-1
	CANT1	ENST00000620915.4	TSL:5	c.*1794T>G		3_prime_UTR	Exon 4 of 4	ENSP00000477798.1	Q8WVQ1-1

Frequencies

GnomAD3 genomes AF: 0.00137 AC: 208 AN: 152280 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00242

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00110 AC: 71 AN: 64322 Hom.: 0 Cov.: 0 AF XY: 0.00113 AC XY: 34 AN XY: 29958

African (AFR) AF: 0.000691 AC: 2 AN: 2894

American (AMR) AF: 0.00 AC: 0 AN: 1914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4082

East Asian (EAS) AF: 0.00 AC: 0 AN: 9514

South Asian (SAS) AF: 0.00 AC: 0 AN: 564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 62

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 386

European-Non Finnish (NFE) AF: 0.00164 AC: 65 AN: 39520

Other (OTH) AF: 0.000743 AC: 4 AN: 5386

GnomAD4 genome AF: 0.00136 AC: 208 AN: 152398 Hom.: 0 Cov.: 33 AF XY: 0.00126 AC XY: 94 AN XY: 74532

African (AFR) AF: 0.000433 AC: 18 AN: 41600

American (AMR) AF: 0.000261 AC: 4 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10632

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

European-Non Finnish (NFE) AF: 0.00242 AC: 165 AN: 68044

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00132 Hom.: 0

Bravo AF: 0.00120

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Desbuquois dysplasia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.55
DANN	Benign	0.55
PhyloP100		-0.17

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: rs192546263; hg19: chr17-76987838;