chr16-28878657-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004320.6(ATP2A1):c.-15C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000788 in 1,585,998 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000080 ( 0 hom. )
Consequence
ATP2A1
NM_004320.6 5_prime_UTR
NM_004320.6 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.837
Genes affected
ATP2A1 (HGNC:811): (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1) This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction. Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Oct 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP2A1 | NM_004320.6 | c.-15C>T | 5_prime_UTR_variant | 1/23 | ENST00000395503.9 | ||
ATP2A1 | NM_173201.5 | c.-15C>T | 5_prime_UTR_variant | 1/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP2A1 | ENST00000395503.9 | c.-15C>T | 5_prime_UTR_variant | 1/23 | 1 | NM_004320.6 | P4 | ||
ATP2A1-AS1 | ENST00000691192.2 | n.1280G>A | non_coding_transcript_exon_variant | 1/1 | |||||
ATP2A1 | ENST00000357084.7 | c.-15C>T | 5_prime_UTR_variant | 1/22 | 2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152160Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000289 AC: 6AN: 207406Hom.: 0 AF XY: 0.0000359 AC XY: 4AN XY: 111488
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GnomAD4 exome AF: 0.0000802 AC: 115AN: 1433838Hom.: 0 Cov.: 30 AF XY: 0.0000675 AC XY: 48AN XY: 710914
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152160Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6AN XY: 74322
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Brody myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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