rs730882252
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_006888.6(CALM1):c.389A>G(p.Asp130Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D130V) has been classified as Likely pathogenic.
Frequency
Consequence
NM_006888.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CALM1 | NM_006888.6 | c.389A>G | p.Asp130Gly | missense_variant | 5/6 | ENST00000356978.9 | |
CALM1 | NM_001363670.2 | c.392A>G | p.Asp131Gly | missense_variant | 5/6 | ||
CALM1 | NM_001363669.2 | c.281A>G | p.Asp94Gly | missense_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CALM1 | ENST00000356978.9 | c.389A>G | p.Asp130Gly | missense_variant | 5/6 | 1 | NM_006888.6 | P1 | |
ENST00000555853.1 | n.44+710T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Long QT syndrome 14 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 05, 2013 | - - |
Pathogenic, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Jul 22, 2020 | This variant is interpreted as pathogenic for Long QT syndrome 14, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3); Assumed de novo, but no confirmation of paternity and maternity (PM6); Well-established functional studies show a deleterious effect (PS3); Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation (PM1). - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 19, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at