chr19-16482520-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_145046.5(CALR3):c.848C>T(p.Thr283Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000231 in 1,614,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T283T) has been classified as Likely benign.
Frequency
Consequence
NM_145046.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CALR3 | NM_145046.5 | c.848C>T | p.Thr283Ile | missense_variant | 7/9 | ENST00000269881.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CALR3 | ENST00000269881.8 | c.848C>T | p.Thr283Ile | missense_variant | 7/9 | 1 | NM_145046.5 | P1 | |
CALR3 | ENST00000602234.1 | n.522C>T | non_coding_transcript_exon_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00132 AC: 201AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000362 AC: 91AN: 251496Hom.: 0 AF XY: 0.000346 AC XY: 47AN XY: 135922
GnomAD4 exome AF: 0.000118 AC: 172AN: 1461884Hom.: 0 Cov.: 46 AF XY: 0.000103 AC XY: 75AN XY: 727244
GnomAD4 genome AF: 0.00132 AC: 201AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.00130 AC XY: 97AN XY: 74480
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 11, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | CALR3 NM_145046.4 exon 7 p.Thr283Ile (c.848C>T): This variant has not been reported in the literature but is present in 0.5% (126/24970) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/19-16593331-G-A). This variant is present in ClinVar (Variation ID:416239). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 10, 2013 | There is insufficient or conflicting evidence for classification of this alteration. - |
Hypertrophic cardiomyopathy 19 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at