rs199957040
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PP2PP3_Moderate
The NM_000388.4(CASR):c.2012A>T(p.Glu671Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. E671D) 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 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASR | NM_000388.4 | c.2012A>T | p.Glu671Val | missense_variant | 7/7 | ENST00000639785.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.2012A>T | p.Glu671Val | missense_variant | 7/7 | 1 | NM_000388.4 | P1 | |
CASR | ENST00000498619.4 | c.2042A>T | p.Glu681Val | missense_variant | 7/7 | 1 | |||
CASR | ENST00000638421.1 | c.2012A>T | p.Glu671Val | missense_variant | 7/7 | 5 | P1 | ||
CASR | ENST00000490131.7 | c.1781A>T | p.Glu594Val | missense_variant | 5/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151478Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251084Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135714
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461302Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 726902
GnomAD4 genome AF: 0.00000660 AC: 1AN: 151478Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73924
ClinVar
Submissions by phenotype
Autosomal dominant hypocalcemia 1;C1809471:Familial hypocalciuric hypercalcemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 07, 2023 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 410338). This variant has not been reported in the literature in individuals affected with CASR-related conditions. This variant is present in population databases (rs199957040, gnomAD 0.0009%). This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 671 of the CASR protein (p.Glu671Val). - |
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 16, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at