19-46608950-C-T
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_005184.4(CALM3):c.390C>T(p.Asp130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,607,656 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0075 ( 17 hom., cov: 32)
Exomes 𝑓: 0.00078 ( 13 hom. )
Consequence
CALM3
NM_005184.4 synonymous
NM_005184.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.64
Genes affected
CALM3 (HGNC:1449): (calmodulin 3) This gene encodes a member of a family of proteins that binds calcium and functions as a enzymatic co-factor. Activity of this protein is important in the regulation of the cell cycle and cytokinesis. Multiple alternatively spliced transcript variants have been observed at this gene. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
Variant 19-46608950-C-T is Benign according to our data. Variant chr19-46608950-C-T is described in ClinVar as [Benign]. Clinvar id is 240118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-46608950-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=2.64 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0075 (1143/152316) while in subpopulation AFR AF= 0.0245 (1020/41566). AF 95% confidence interval is 0.0233. There are 17 homozygotes in gnomad4. There are 530 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1143 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CALM3 | NM_005184.4 | c.390C>T | p.Asp130= | synonymous_variant | 5/6 | ENST00000291295.14 | |
LOC124904729 | XR_007067276.1 | n.119G>A | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CALM3 | ENST00000291295.14 | c.390C>T | p.Asp130= | synonymous_variant | 5/6 | 1 | NM_005184.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00746 AC: 1135AN: 152198Hom.: 17 Cov.: 32
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GnomAD3 exomes AF: 0.00193 AC: 471AN: 244256Hom.: 5 AF XY: 0.00143 AC XY: 188AN XY: 131926
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GnomAD4 exome AF: 0.000783 AC: 1140AN: 1455340Hom.: 13 Cov.: 32 AF XY: 0.000665 AC XY: 481AN XY: 723598
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GnomAD4 genome AF: 0.00750 AC: 1143AN: 152316Hom.: 17 Cov.: 32 AF XY: 0.00712 AC XY: 530AN XY: 74476
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 12, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 21, 2024 | - - |
Long QT syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Long QT syndrome 16 Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 27, 2021 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 04, 2019 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at