Genetic Variant CANT1:c.*876G>A (chr17-78992674-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001159773.2(CANT1):c.*876G>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 0.000102 in 586,944 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

CANT1
NM_001159773.2 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

Publications

0 publications found

Variant links:

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

CANT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CANT1	NM_001159773.2	MANE Select	c.*876G>A	3_prime_UTR	Exon 5 of 5	NP_001153245.1	Q8WVQ1-1
CANT1	NM_001159772.2		c.*876G>A	3_prime_UTR	Exon 6 of 6	NP_001153244.1	Q8WVQ1-1
CANT1	NM_138793.4		c.*876G>A	3_prime_UTR	Exon 4 of 4	NP_620148.1	Q8WVQ1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CANT1	ENST00000392446.10	TSL:1 MANE Select	c.*876G>A	3_prime_UTR	Exon 5 of 5	ENSP00000376241.4	Q8WVQ1-1
CANT1	ENST00000302345.6	TSL:2	c.*876G>A	3_prime_UTR	Exon 4 of 4	ENSP00000307674.2	Q8WVQ1-1
CANT1	ENST00000620915.4	TSL:5	c.*876G>A	3_prime_UTR	Exon 4 of 4	ENSP00000477798.1	Q8WVQ1-1

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.0000776

AC:

AN:

218974

AF XY:

0.0000990

show subpopulations

Gnomad AFR exome

AF:

0.0000752

Gnomad AMR exome

AF:

0.000351

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000290

Gnomad OTH exome

AF:

0.000355

GnomAD4 exome

AF:

0.0000667

AC:

AN:

434638

Hom.:

Cov.:

AF XY:

0.0000706

AC XY:

AN XY:

240788

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13570

American (AMR)

AF:

0.000449

AC:

AN:

35640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16310

East Asian (EAS)

AF:

0.00

AC:

AN:

24136

South Asian (SAS)

AF:

0.00

AC:

AN:

65664

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16590

Middle Eastern (MID)

AF:

0.000305

AC:

AN:

3274

European-Non Finnish (NFE)

AF:

0.0000338

AC:

AN:

236692

Other (OTH)

AF:

0.000176

AC:

AN:

22762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000204

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41566

American (AMR)

AF:

0.00137

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000295

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Desbuquois dysplasia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.5

(source)

DANN

Benign

0.85

PhyloP100

1.8

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over