Variant rs267606699 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5

The NM_001159773.2(CANT1):c.899G>A(p.Arg300His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000376 in 1,597,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R300C) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CANT1
NM_001159773.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.42

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PM1

In a strand (size 5) in uniprot entity CANT1_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_001159773.2

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr17-78993858-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.994

PP5

Variant 17-78993857-C-T is Pathogenic according to our data. Variant chr17-78993857-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 280.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CANT1	NM_001159773.2 linkuse as main transcript	c.899G>A	p.Arg300His	missense_variant	5/5	ENST00000392446.10
CANT1	NM_001159772.2 linkuse as main transcript	c.899G>A	p.Arg300His	missense_variant	6/6
CANT1	NM_138793.4 linkuse as main transcript	c.899G>A	p.Arg300His	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CANT1	ENST00000392446.10 linkuse as main transcript	c.899G>A	p.Arg300His	missense_variant	5/5	1	NM_001159773.2	P1	Q8WVQ1-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD3 exomes

AF:

0.00000435

AC:

AN:

229990

Hom.:

AF XY:

0.00000793

AC XY:

AN XY:

126126

show subpopulations

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:

0.0000337

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000346

AC:

AN:

1445548

Hom.:

Cov.:

AF XY:

0.00000418

AC XY:

AN XY:

718288

show subpopulations

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Desbuquois dysplasia 1

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.51

BayesDel_noAF

Pathogenic

0.50

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.94

D;D;D;D

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

D;.;.;.

M_CAP

Pathogenic

0.68

MetaRNN

Pathogenic

0.99

D;D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.9

H;H;H;H

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.8

.;D;D;.

REVEL

Pathogenic

0.93

Sift

Pathogenic

0.0

.;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.78

MutPred

0.98

Loss of MoRF binding (P = 0.0353);Loss of MoRF binding (P = 0.0353);Loss of MoRF binding (P = 0.0353);Loss of MoRF binding (P = 0.0353);

MVP

1.0

MPC

1.2

ClinPred

1.0

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.93

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over