rs1220477298
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM5PP2PP3_Moderate
The NM_000388.4(CASR):āc.512G>Cā(p.Ser171Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S171R) has been classified as Uncertain significance.
Frequency
Consequence
NM_000388.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASR | NM_000388.4 | c.512G>C | p.Ser171Thr | missense_variant | 4/7 | ENST00000639785.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.512G>C | p.Ser171Thr | missense_variant | 4/7 | 1 | NM_000388.4 | P1 | |
CASR | ENST00000498619.4 | c.512G>C | p.Ser171Thr | missense_variant | 4/7 | 1 | |||
CASR | ENST00000638421.1 | c.512G>C | p.Ser171Thr | missense_variant | 4/7 | 5 | P1 | ||
CASR | ENST00000490131.7 | c.512G>C | p.Ser171Thr | missense_variant | 3/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
Nephrolithiasis/nephrocalcinosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 27, 2023 | The p.S171T variant (also known as c.512G>C), located in coding exon 3 of the CASR gene, results from a G to C substitution at nucleotide position 512. The serine at codon 171 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious 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 | Invitae | Oct 13, 2023 | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 171 of the CASR protein (p.Ser171Thr). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 532593). 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 disruptive. 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