rs1392565832
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000070.3(CAPN3):c.51C>T(p.Pro17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
CAPN3
NM_000070.3 synonymous
NM_000070.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.799
Genes affected
CAPN3 (HGNC:1480): (calpain 3) Calpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene encodes a muscle-specific member of the calpain large subunit family that specifically binds to titin. Mutations in this gene are associated with limb-girdle muscular dystrophies type 2A. Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 15-42359856-C-T is Benign according to our data. Variant chr15-42359856-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 468651.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.799 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAPN3 | NM_000070.3 | c.51C>T | p.Pro17= | synonymous_variant | 1/24 | ENST00000397163.8 | |
CAPN3 | NM_024344.2 | c.51C>T | p.Pro17= | synonymous_variant | 1/23 | ||
CAPN3 | NM_173087.2 | c.51C>T | p.Pro17= | synonymous_variant | 1/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN3 | ENST00000397163.8 | c.51C>T | p.Pro17= | synonymous_variant | 1/24 | 1 | NM_000070.3 | P2 | |
CAPN3 | ENST00000357568.8 | c.51C>T | p.Pro17= | synonymous_variant | 1/23 | 1 | |||
CAPN3 | ENST00000349748.8 | c.51C>T | p.Pro17= | synonymous_variant | 1/21 | 1 | |||
CAPN3 | ENST00000318023.11 | c.51C>T | p.Pro17= | synonymous_variant | 1/23 | 5 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250626Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135768
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461840Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727226
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 19, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at