rs202101164
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_000388.4(CASR):c.1193A>G(p.Asp398Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000291 in 1,613,986 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 (★★).
Frequency
Consequence
NM_000388.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.1193A>G | p.Asp398Gly | missense_variant | Exon 4 of 7 | 1 | NM_000388.4 | ENSP00000491584.2 | ||
CASR | ENST00000498619.4 | c.1193A>G | p.Asp398Gly | missense_variant | Exon 4 of 7 | 1 | ENSP00000420194.1 | |||
CASR | ENST00000638421.1 | c.1193A>G | p.Asp398Gly | missense_variant | Exon 4 of 7 | 5 | ENSP00000492190.1 | |||
CASR | ENST00000490131.7 | c.1193A>G | p.Asp398Gly | missense_variant | Exon 3 of 5 | 5 | ENSP00000418685.2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251438Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135888
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461796Hom.: 0 Cov.: 33 AF XY: 0.0000316 AC XY: 23AN XY: 727200
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354
ClinVar
Submissions by phenotype
Nephrolithiasis/nephrocalcinosis Uncertain:1
The p.D398G variant (also known as c.1193A>G), located in coding exon 3 of the CASR gene, results from an A to G substitution at nucleotide position 1193. The aspartic acid at codon 398 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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. -
CASR-related disorder Uncertain:1
The CASR c.1193A>G variant is predicted to result in the amino acid substitution p.Asp398Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0053% of alleles in individuals of European (non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Autosomal dominant hypocalcemia 1;C1809471:Familial hypocalciuric hypercalcemia Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 398 of the CASR protein (p.Asp398Gly). This variant is present in population databases (rs202101164, gnomAD 0.005%). 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: 573275). 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 tolerated. 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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at