chr17-78993860-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_001159773.2(CANT1):c.896C>T(p.Pro299Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000751 in 1,597,880 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 Likely pathogenic (★).
Frequency
Consequence
NM_001159773.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CANT1 | NM_001159773.2 | c.896C>T | p.Pro299Leu | missense_variant | Exon 5 of 5 | ENST00000392446.10 | NP_001153245.1 | |
CANT1 | NM_001159772.2 | c.896C>T | p.Pro299Leu | missense_variant | Exon 6 of 6 | NP_001153244.1 | ||
CANT1 | NM_138793.4 | c.896C>T | p.Pro299Leu | missense_variant | Exon 4 of 4 | NP_620148.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000437 AC: 1AN: 229040Hom.: 0 AF XY: 0.00000795 AC XY: 1AN XY: 125764
GnomAD4 exome AF: 0.00000692 AC: 10AN: 1445632Hom.: 0 Cov.: 31 AF XY: 0.00000835 AC XY: 6AN XY: 718484
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Submissions by phenotype
Desbuquois dysplasia 1 Pathogenic:2
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The homozygous mis-sense variant c.896C>T (p.P299L) has been previously reported by Huber C et al in 2009 as a heterozygous variant in a Brazilian patient. The allele frequency is 0.0004% in gnomAD (aggregated) database. In-silico bioinformatic software predict this variant by mutation taster as Disease causing and SIFT & PROVEAN as Damaging. The phenotype observed was mesomelic shortening of limbs, cystic hygroma, hypoplastic pulmonary artery, hypoplastic lungs, cleft palate, renal cysts, non-immune fetal hydrops. Desbuquois Dysplasia 1 is an autosomal recessive disorder. Based on the phenotypic observation, we classify this variant as likely pathogenic. -
CANT1-related disorder Pathogenic:1
The CANT1 c.896C>T variant is predicted to result in the amino acid substitution p.Pro299Leu. This variant along with a second variant in this gene was reported in two children in one in family with Desbuquois dysplasia (Huber et al. 2009. PubMed ID: 19853239) and found in the homozygous condition in another individual with Desbuquois dysplasia (Biji et al. 2023. PubMed ID: 36331722). This variant is reported in 0.0057% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-76989942-G-A). This variant is interpreted as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at