chr3-122285012-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The ENST00000639785.2(CASR):āc.3058G>Cā(p.Glu1020Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,614,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
ENST00000639785.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CASR | NM_000388.4 | c.3058G>C | p.Glu1020Gln | missense_variant | 7/7 | ENST00000639785.2 | NP_000379.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.3058G>C | p.Glu1020Gln | missense_variant | 7/7 | 1 | NM_000388.4 | ENSP00000491584 | P1 | |
CASR | ENST00000498619.4 | c.3088G>C | p.Glu1030Gln | missense_variant | 7/7 | 1 | ENSP00000420194 | |||
CASR | ENST00000638421.1 | c.3058G>C | p.Glu1020Gln | missense_variant | 7/7 | 5 | ENSP00000492190 | P1 | ||
CASR | ENST00000490131.7 | c.2827G>C | p.Glu943Gln | missense_variant | 5/5 | 5 | ENSP00000418685 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461888Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1AN XY: 727246
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74374
ClinVar
Submissions by phenotype
Nephrolithiasis/nephrocalcinosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 30, 2023 | The p.E1020Q variant (also known as c.3058G>C), located in coding exon 6 of the CASR gene, results from a G to C substitution at nucleotide position 3058. The glutamic acid at codon 1020 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 12, 2023 | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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. ClinVar contains an entry for this variant (Variation ID: 410353). This variant has not been reported in the literature in individuals affected with CASR-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 1020 of the CASR protein (p.Glu1020Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at