rs752021942
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004320.6(ATP2A1):c.1294G>A(p.Gly432Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,440 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G432G) has been classified as Likely benign.
Frequency
Consequence
NM_004320.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP2A1 | NM_004320.6 | c.1294G>A | p.Gly432Ser | missense_variant | 12/23 | ENST00000395503.9 | |
ATP2A1 | NM_173201.5 | c.1294G>A | p.Gly432Ser | missense_variant | 12/22 | ||
ATP2A1 | NM_001286075.2 | c.919G>A | p.Gly307Ser | missense_variant | 10/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP2A1 | ENST00000395503.9 | c.1294G>A | p.Gly432Ser | missense_variant | 12/23 | 1 | NM_004320.6 | P4 | |
ATP2A1 | ENST00000357084.7 | c.1294G>A | p.Gly432Ser | missense_variant | 12/22 | 2 | A1 | ||
ATP2A1 | ENST00000536376.5 | c.919G>A | p.Gly307Ser | missense_variant | 10/21 | 2 | |||
ATP2A1 | ENST00000564732.1 | c.324G>A | p.Lys108= | synonymous_variant, NMD_transcript_variant | 4/7 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249318Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134870
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459440Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 726052
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Brody myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This variant has not been reported in the literature in individuals affected with ATP2A1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 464072). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 432 of the ATP2A1 protein (p.Gly432Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at