rs1553769153
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP2PP3
The ENST00000639785.2(CASR):āc.2635C>Gā(p.His879Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,268 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 ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H879Q) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000639785.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CASR | NM_000388.4 | c.2635C>G | p.His879Asp | 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.2635C>G | p.His879Asp | missense_variant | 7/7 | 1 | NM_000388.4 | ENSP00000491584 | P1 | |
CASR | ENST00000498619.4 | c.2665C>G | p.His889Asp | missense_variant | 7/7 | 1 | ENSP00000420194 | |||
CASR | ENST00000638421.1 | c.2635C>G | p.His879Asp | missense_variant | 7/7 | 5 | ENSP00000492190 | P1 | ||
CASR | ENST00000490131.7 | c.2404C>G | p.His802Asp | missense_variant | 5/5 | 5 | ENSP00000418685 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152268Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 70
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152268Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74396
ClinVar
Submissions by phenotype
Autosomal dominant hypocalcemia 1;C1809471:Familial hypocalciuric hypercalcemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 10, 2017 | 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with CASR-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with aspartic acid at codon 879 of the CASR protein (p.His879Asp). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at