chr3-122284592-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM1PP2BP4
The NM_000388.4(CASR):c.2638G>T(p.Ala880Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A880P) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASR | NM_000388.4 | c.2638G>T | p.Ala880Ser | missense_variant | 7/7 | ENST00000639785.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.2638G>T | p.Ala880Ser | missense_variant | 7/7 | 1 | NM_000388.4 | P1 | |
CASR | ENST00000498619.4 | c.2668G>T | p.Ala890Ser | missense_variant | 7/7 | 1 | |||
CASR | ENST00000638421.1 | c.2638G>T | p.Ala880Ser | missense_variant | 7/7 | 5 | P1 | ||
CASR | ENST00000490131.7 | c.2407G>T | p.Ala803Ser | missense_variant | 5/5 | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251114Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135814
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461822Hom.: 0 Cov.: 70 AF XY: 0.00000550 AC XY: 4AN XY: 727222
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Nephrolithiasis/nephrocalcinosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 26, 2021 | The p.A880S variant (also known as c.2638G>T), located in coding exon 6 of the CASR gene, results from a G to T substitution at nucleotide position 2638. The alanine at codon 880 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. 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 | Jan 13, 2024 | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 880 of the CASR protein (p.Ala880Ser). This variant is present in population databases (rs763865303, gnomAD 0.01%). 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: 653245). 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. - |
Autosomal dominant hypocalcemia 1;C0342637:Familial hypocalciuric hypercalcemia 1;C1832615:Neonatal severe primary hyperparathyroidism;C2752062:Epilepsy, idiopathic generalized, susceptibility to, 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 03, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at