chr19-16479153-AATTG-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_145046.5(CALR3):c.1129_1132del(p.Gln377PhefsTer14) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q377Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_145046.5 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CALR3 | NM_145046.5 | c.1129_1132del | p.Gln377PhefsTer14 | frameshift_variant | 9/9 | ENST00000269881.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CALR3 | ENST00000269881.8 | c.1129_1132del | p.Gln377PhefsTer14 | frameshift_variant | 9/9 | 1 | NM_145046.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251486Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135920
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461876Hom.: 0 AF XY: 0.0000110 AC XY: 8AN XY: 727242
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74302
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy 19 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 573600). This variant has not been reported in the literature in individuals affected with CALR3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change results in a frameshift in the CALR3 gene (p.Gln377Phefs*14). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 8 amino acid(s) of the CALR3 protein and extend the protein by 5 additional amino acid residues. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at