rs141934227
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000070.3(CAPN3):c.1017G>A(p.Thr339=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,613,690 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00026 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00034 ( 7 hom. )
Consequence
CAPN3
NM_000070.3 synonymous
NM_000070.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.47
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 15-42392710-G-A is Benign according to our data. Variant chr15-42392710-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 288393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-42392710-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-2.47 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 7 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAPN3 | NM_000070.3 | c.1017G>A | p.Thr339= | synonymous_variant | 7/24 | ENST00000397163.8 | |
CAPN3 | NM_024344.2 | c.1017G>A | p.Thr339= | synonymous_variant | 7/23 | ||
CAPN3 | NM_173087.2 | c.873G>A | p.Thr291= | synonymous_variant | 6/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN3 | ENST00000397163.8 | c.1017G>A | p.Thr339= | synonymous_variant | 7/24 | 1 | NM_000070.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000263 AC: 40AN: 152176Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000630 AC: 158AN: 250976Hom.: 3 AF XY: 0.000877 AC XY: 119AN XY: 135682
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GnomAD4 exome AF: 0.000345 AC: 504AN: 1461396Hom.: 7 Cov.: 31 AF XY: 0.000475 AC XY: 345AN XY: 727016
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GnomAD4 genome ? AF: 0.000256 AC: 39AN: 152294Hom.: 1 Cov.: 32 AF XY: 0.000363 AC XY: 27AN XY: 74468
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 31, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 29, 2018 | 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. - |
Autosomal recessive limb-girdle muscular dystrophy type 2A Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 09, 2019 | - - |
Computational scores
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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