17-78992383-C-T

Variant names:

• chr17-78992383-C-T
• rs186436891
• NM_001159773.2:c.*1167G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_001159773.2(CANT1):​c.*1167G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00986 in 282,022 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (11 hom., cov: 32)
  • Exomes 𝑓: 0.011 (15 hom.)
• Consequence: CANT1 NM_001159773.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.394
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00892 (1359/152270) while in subpopulation NFE AF = 0.0146 (994/68024). AF 95% confidence interval is 0.0139. There are 11 homozygotes in GnomAd4. There are 584 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 11 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CANT1	NM_001159773.2	MANE Select	c.*1167G>A		3_prime_UTR	Exon 5 of 5	NP_001153245.1	Q8WVQ1-1
	CANT1	NM_001159772.2		c.*1167G>A		3_prime_UTR	Exon 6 of 6	NP_001153244.1	Q8WVQ1-1
	CANT1	NM_138793.4		c.*1167G>A		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.*1167G>A		3_prime_UTR	Exon 5 of 5	ENSP00000376241.4	Q8WVQ1-1
	CANT1	ENST00000302345.6	TSL:2	c.*1167G>A		3_prime_UTR	Exon 4 of 4	ENSP00000307674.2	Q8WVQ1-1
	CANT1	ENST00000620915.4	TSL:5	c.*1167G>A		3_prime_UTR	Exon 4 of 4	ENSP00000477798.1	Q8WVQ1-1

Frequencies

GnomAD3 genomes AF: 0.00893 AC: 1358 AN: 152152 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00297

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.0110 AC: 1422 AN: 129752 Hom.: 15 Cov.: 0 AF XY: 0.0105 AC XY: 673 AN XY: 64244

African (AFR) AF: 0.00227 AC: 13 AN: 5738

American (AMR) AF: 0.00800 AC: 49 AN: 6128

Ashkenazi Jewish (ASJ) AF: 0.0108 AC: 67 AN: 6202

East Asian (EAS) AF: 0.0000735 AC: 1 AN: 13604

South Asian (SAS) AF: 0.00193 AC: 19 AN: 9842

European-Finnish (FIN) AF: 0.00292 AC: 6 AN: 2052

Middle Eastern (MID) AF: 0.00915 AC: 6 AN: 656

European-Non Finnish (NFE) AF: 0.0154 AC: 1174 AN: 76482

Other (OTH) AF: 0.00962 AC: 87 AN: 9048

GnomAD4 genome AF: 0.00892 AC: 1359 AN: 152270 Hom.: 11 Cov.: 32 AF XY: 0.00784 AC XY: 584 AN XY: 74446

African (AFR) AF: 0.00296 AC: 123 AN: 41550

American (AMR) AF: 0.00981 AC: 150 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 28 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4822

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0146 AC: 994 AN: 68024

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.0110 Hom.: 1

Bravo AF: 0.00926

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Desbuquois dysplasia 1 (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.81
PhyloP100		0.39
Mutation Taster		=100/0	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: rs186436891; hg19: chr17-76988465;