rs2377301

Variant names:

• chr17-78998287-C-T
• rs2377301
• NM_001159773.2:c.-146-324G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 8P and 8B. PVS1 BA1

The NM_001159772.2(CANT1):​c.-285-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 157,274 control chromosomes in the GnomAD database, including 1,761 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (1709 hom., cov: 33)
  • Exomes 𝑓: 0.14 (52 hom.)
• Consequence: CANT1 NM_001159772.2 splice_acceptor, intron
• Scores: Splicing: ADA: 0.0001073
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346
• Publications: 14 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: Uncertain_significance. The variant received 0 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159772.2. 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.-146-324G>A		intron	N/A	NP_001153245.1	Q8WVQ1-1
	CANT1	NM_001159772.2		c.-285-1G>A		splice_acceptor intron	N/A	NP_001153244.1	Q8WVQ1-1
	CANT1	NM_138793.4		c.-341-324G>A		intron	N/A	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.-146-324G>A		intron	N/A	ENSP00000376241.4	Q8WVQ1-1
	CANT1	ENST00000591773.5	TSL:1	c.-285-1G>A		splice_acceptor intron	N/A	ENSP00000467437.1	Q8WVQ1-1
	CANT1	ENST00000620915.4	TSL:5	c.-292G>A		5_prime_UTR	Exon 1 of 4	ENSP00000477798.1	Q8WVQ1-1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20019 AN: 152158 Hom.: 1700 Cov.: 33

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.138 AC: 690 AN: 4998 Hom.: 52 Cov.: 0 AF XY: 0.135 AC XY: 326 AN XY: 2422

African (AFR) AF: 0.0493 AC: 7 AN: 142

American (AMR) AF: 0.293 AC: 41 AN: 140

Ashkenazi Jewish (ASJ) AF: 0.0678 AC: 24 AN: 354

East Asian (EAS) AF: 0.253 AC: 240 AN: 950

South Asian (SAS) AF: 0.143 AC: 4 AN: 28

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AF: 0.0294 AC: 1 AN: 34

European-Non Finnish (NFE) AF: 0.109 AC: 317 AN: 2906

Other (OTH) AF: 0.125 AC: 55 AN: 440

GnomAD4 genome AF: 0.132 AC: 20030 AN: 152276 Hom.: 1709 Cov.: 33 AF XY: 0.136 AC XY: 10142 AN XY: 74448

African (AFR) AF: 0.0947 AC: 3935 AN: 41560

American (AMR) AF: 0.253 AC: 3874 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 266 AN: 3472

East Asian (EAS) AF: 0.302 AC: 1565 AN: 5182

South Asian (SAS) AF: 0.236 AC: 1139 AN: 4830

European-Finnish (FIN) AF: 0.0931 AC: 988 AN: 10614

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7775 AN: 68012

Other (OTH) AF: 0.129 AC: 272 AN: 2114

Alfa AF: 0.126 Hom.: 913

Bravo AF: 0.141

Asia WGS AF: 0.266 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.3
DANN	Benign	0.85
PhyloP100		0.35
PromoterAI		0.059	Neutral
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.0060
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: rs2377301; hg19: chr17-76994369;