2-30743552-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_144575.3(CAPN13):c.1276T>C(p.Phe426Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
CAPN13
NM_144575.3 missense
NM_144575.3 missense
Scores
3
5
11
Clinical Significance
Conservation
PhyloP100: 3.50
Genes affected
CAPN13 (HGNC:16663): (calpain 13) The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes a member of the calpain large subunit family. [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.85
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAPN13 | NM_144575.3 | c.1276T>C | p.Phe426Leu | missense_variant | 13/23 | ENST00000295055.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN13 | ENST00000295055.12 | c.1276T>C | p.Phe426Leu | missense_variant | 13/23 | 5 | NM_144575.3 | P1 | |
CAPN13 | ENST00000465450.2 | n.164T>C | non_coding_transcript_exon_variant | 3/3 | 5 | ||||
CAPN13 | ENST00000458085.6 | c.1249-17T>C | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 5 | |||||
CAPN13 | ENST00000450650.5 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249216Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135214
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461702Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727132
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74354
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 06, 2022 | The c.1276T>C (p.F426L) alteration is located in exon 13 (coding exon 12) of the CAPN13 gene. This alteration results from a T to C substitution at nucleotide position 1276, causing the phenylalanine (F) at amino acid position 426 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of loop (P = 0.0851);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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