rs199688157
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_000388.4(CASR):c.1573G>A(p.Glu525Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,578 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E525A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000388.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASR | NM_000388.4 | c.1573G>A | p.Glu525Lys | missense_variant | 5/7 | ENST00000639785.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.1573G>A | p.Glu525Lys | missense_variant | 5/7 | 1 | NM_000388.4 | P1 | |
CASR | ENST00000498619.4 | c.1573G>A | p.Glu525Lys | missense_variant | 5/7 | 1 | |||
CASR | ENST00000638421.1 | c.1573G>A | p.Glu525Lys | missense_variant | 5/7 | 5 | P1 | ||
CASR | ENST00000490131.7 | c.1378-6106G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251168Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135738
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461400Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727048
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74342
ClinVar
Submissions by phenotype
Nephrolithiasis/nephrocalcinosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 17, 2023 | The p.E525K variant (also known as c.1573G>A), located in coding exon 4 of the CASR gene, results from a G to A substitution at nucleotide position 1573. The glutamic acid at codon 525 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and lysine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Autosomal dominant hypocalcemia 1;C1809471:Familial hypocalciuric hypercalcemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 29, 2023 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 525 of the CASR protein (p.Glu525Lys). This variant is present in population databases (rs199688157, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CASR-related conditions. ClinVar contains an entry for this variant (Variation ID: 463907). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at