chr3-122275846-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The ENST00000639785.2(CASR):c.1412A>T(p.Asn471Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. N471N) has been classified as Likely benign.
Frequency
Consequence
ENST00000639785.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CASR | NM_000388.4 | c.1412A>T | p.Asn471Ile | missense_variant | 5/7 | ENST00000639785.2 | NP_000379.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.1412A>T | p.Asn471Ile | missense_variant | 5/7 | 1 | NM_000388.4 | ENSP00000491584 | P1 | |
CASR | ENST00000498619.4 | c.1412A>T | p.Asn471Ile | missense_variant | 5/7 | 1 | ENSP00000420194 | |||
CASR | ENST00000638421.1 | c.1412A>T | p.Asn471Ile | missense_variant | 5/7 | 5 | ENSP00000492190 | P1 | ||
CASR | ENST00000490131.7 | c.1378-6267A>T | intron_variant | 5 | ENSP00000418685 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251436Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135894
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461798Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727216
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74314
ClinVar
Submissions by phenotype
Nephrolithiasis/nephrocalcinosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 05, 2023 | The p.N471I variant (also known as c.1412A>T), located in coding exon 4 of the CASR gene, results from an A to T substitution at nucleotide position 1412. The asparagine at codon 471 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is 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. - |
Autosomal dominant hypocalcemia 1;C1809471:Familial hypocalciuric hypercalcemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 02, 2023 | This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 471 of the CASR protein (p.Asn471Ile). This variant is present in population databases (rs145042469, gnomAD 0.002%). 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: 566997). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 09, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at