chr3-122254210-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_000388.4(CASR):c.21C>G(p.Cys7Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. C7F) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASR | NM_000388.4 | c.21C>G | p.Cys7Trp | missense_variant | 2/7 | ENST00000639785.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.21C>G | p.Cys7Trp | missense_variant | 2/7 | 1 | NM_000388.4 | P1 | |
CASR | ENST00000498619.4 | c.21C>G | p.Cys7Trp | missense_variant | 2/7 | 1 | |||
CASR | ENST00000638421.1 | c.21C>G | p.Cys7Trp | missense_variant | 2/7 | 5 | P1 | ||
CASR | ENST00000490131.7 | c.21C>G | p.Cys7Trp | missense_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251344Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135830
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461034Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726804
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Nephrolithiasis/nephrocalcinosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 20, 2019 | The p.C7W variant (also known as c.21C>G), located in coding exon 1 of the CASR gene, results from a C to G substitution at nucleotide position 21. The cysteine at codon 7 is replaced by tryptophan, an amino acid with highly dissimilar 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at