rs577190575
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_004320.6(ATP2A1):c.1218G>A(p.Gln406=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000867 in 1,614,130 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: 𝑓 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
ATP2A1
NM_004320.6 synonymous
NM_004320.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.26
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 Benign. Variant got -10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 16-28894538-G-A is Benign according to our data. Variant chr16-28894538-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 464070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP2A1 | NM_004320.6 | c.1218G>A | p.Gln406= | synonymous_variant | 11/23 | ENST00000395503.9 | |
ATP2A1 | NM_173201.5 | c.1218G>A | p.Gln406= | synonymous_variant | 11/22 | ||
ATP2A1 | NM_001286075.2 | c.843G>A | p.Gln281= | synonymous_variant | 9/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP2A1 | ENST00000395503.9 | c.1218G>A | p.Gln406= | synonymous_variant | 11/23 | 1 | NM_004320.6 | P4 | |
ATP2A1 | ENST00000357084.7 | c.1218G>A | p.Gln406= | synonymous_variant | 11/22 | 2 | A1 | ||
ATP2A1 | ENST00000536376.5 | c.843G>A | p.Gln281= | synonymous_variant | 9/21 | 2 | |||
ATP2A1 | ENST00000564732.1 | c.317-284G>A | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152182Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251318Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135838
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461830Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727220
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152300Hom.: 0 Cov.: 31 AF XY: 0.0000806 AC XY: 6AN XY: 74474
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Brody myopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 11, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 01, 2021 | - - |
Computational scores
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Name
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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