3-122261786-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_000388.4(CASR):c.751G>C(p.Glu251Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000388.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.751G>C | p.Glu251Gln | missense_variant | Exon 4 of 7 | 1 | NM_000388.4 | ENSP00000491584.2 | ||
CASR | ENST00000498619.4 | c.751G>C | p.Glu251Gln | missense_variant | Exon 4 of 7 | 1 | ENSP00000420194.1 | |||
CASR | ENST00000638421.1 | c.751G>C | p.Glu251Gln | missense_variant | Exon 4 of 7 | 5 | ENSP00000492190.1 | |||
CASR | ENST00000490131.7 | c.751G>C | p.Glu251Gln | missense_variant | Exon 3 of 5 | 5 | ENSP00000418685.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 34
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Autosomal dominant hypocalcemia 1;C1809471:Familial hypocalciuric hypercalcemia Uncertain:1
In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CASR-related disease. This sequence change replaces glutamic acid with glutamine at codon 251 of the CASR protein (p.Glu251Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at