16-546893-G-A
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_005632.3(CAPN15):c.55G>A(p.Gly19Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,611,540 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00019 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000038 ( 1 hom. )
Consequence
CAPN15
NM_005632.3 missense
NM_005632.3 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 8.01
Genes affected
CAPN15 (HGNC:11182): (calpain 15) This gene encodes a protein containing zinc-finger-like repeats and a calpain-like protease domain. The encoded protein may function as a transcription factor, RNA-binding protein, or in protein-protein interactions during visual system development. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.104115814).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00019 (29/152354) while in subpopulation AFR AF= 0.000529 (22/41578). AF 95% confidence interval is 0.000358. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CAPN15 | NM_005632.3 | c.55G>A | p.Gly19Ser | missense_variant | 4/14 | ENST00000219611.7 | NP_005623.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CAPN15 | ENST00000219611.7 | c.55G>A | p.Gly19Ser | missense_variant | 4/14 | 1 | NM_005632.3 | ENSP00000219611 | P1 | |
CAPN15 | ENST00000637507.1 | c.259G>A | p.Gly87Ser | missense_variant | 2/2 | 5 | ENSP00000490480 | |||
CAPN15 | ENST00000562370.5 | c.55G>A | p.Gly19Ser | missense_variant | 3/3 | 2 | ENSP00000456017 | |||
CAPN15 | ENST00000568988.5 | c.-314-666G>A | intron_variant | 3 | ENSP00000457030 |
Frequencies
GnomAD3 genomes AF: 0.000190 AC: 29AN: 152236Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000532 AC: 13AN: 244498Hom.: 0 AF XY: 0.0000299 AC XY: 4AN XY: 133790
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GnomAD4 exome AF: 0.0000377 AC: 55AN: 1459186Hom.: 1 Cov.: 32 AF XY: 0.0000317 AC XY: 23AN XY: 725982
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GnomAD4 genome AF: 0.000190 AC: 29AN: 152354Hom.: 0 Cov.: 34 AF XY: 0.000148 AC XY: 11AN XY: 74480
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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 | Dec 28, 2022 | The c.55G>A (p.G19S) alteration is located in exon 4 (coding exon 1) of the CAPN15 gene. This alteration results from a G to A substitution at nucleotide position 55, causing the glycine (G) at amino acid position 19 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Benign
T;D;.
Sift4G
Uncertain
T;T;.
Polyphen
0.98
.;D;.
Vest4
0.65
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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