chr3-122275944-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM1PM2PP2BP4_Moderate
The NM_000388.4(CASR):c.1510G>C(p.Val504Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V504M) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASR | NM_000388.4 | c.1510G>C | p.Val504Leu | missense_variant | 5/7 | ENST00000639785.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.1510G>C | p.Val504Leu | missense_variant | 5/7 | 1 | NM_000388.4 | P1 | |
CASR | ENST00000498619.4 | c.1510G>C | p.Val504Leu | missense_variant | 5/7 | 1 | |||
CASR | ENST00000638421.1 | c.1510G>C | p.Val504Leu | missense_variant | 5/7 | 5 | P1 | ||
CASR | ENST00000490131.7 | c.1378-6169G>C | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152238Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74496
ClinVar
Submissions by phenotype
Autosomal dominant hypocalcemia 1;C1809471:Familial hypocalciuric hypercalcemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2022 | This variant has not been reported in the literature in individuals affected with CASR-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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). ClinVar contains an entry for this variant (Variation ID: 639212). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 504 of the CASR protein (p.Val504Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at