rs775066593
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_000388.4(CASR):c.3220A>G(p.Asn1074Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000564 in 1,614,082 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★★). Synonymous variant affecting the same amino acid position (i.e. N1074N) has been classified as Likely benign.
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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASR | NM_000388.4 | c.3220A>G | p.Asn1074Asp | missense_variant | 7/7 | ENST00000639785.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.3220A>G | p.Asn1074Asp | missense_variant | 7/7 | 1 | NM_000388.4 | P1 | |
CASR | ENST00000498619.4 | c.3250A>G | p.Asn1084Asp | missense_variant | 7/7 | 1 | |||
CASR | ENST00000638421.1 | c.3220A>G | p.Asn1074Asp | missense_variant | 7/7 | 5 | P1 | ||
CASR | ENST00000490131.7 | c.2989A>G | p.Asn997Asp | missense_variant | 5/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249680Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135456
GnomAD4 exome AF: 0.0000588 AC: 86AN: 1461808Hom.: 1 Cov.: 37 AF XY: 0.0000523 AC XY: 38AN XY: 727208
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74472
ClinVar
Submissions by phenotype
Nephrolithiasis/nephrocalcinosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 02, 2023 | The p.N1074D variant (also known as c.3220A>G), located in coding exon 6 of the CASR gene, results from an A to G substitution at nucleotide position 3220. The asparagine at codon 1074 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly 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 | Invitae | Nov 04, 2023 | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 1074 of the CASR protein (p.Asn1074Asp). This variant is present in population databases (rs775066593, gnomAD 0.006%). 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: 463949). 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
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 15, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at