chr3-122284163-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM1PP2BP4_ModerateBP6
The NM_000388.4(CASR):c.2209G>A(p.Val737Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000388.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CASR | NM_000388.4 | c.2209G>A | p.Val737Ile | missense_variant | 7/7 | ENST00000639785.2 | NP_000379.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.2209G>A | p.Val737Ile | missense_variant | 7/7 | 1 | NM_000388.4 | ENSP00000491584.2 | ||
CASR | ENST00000498619.4 | c.2239G>A | p.Val747Ile | missense_variant | 7/7 | 1 | ENSP00000420194.1 | |||
CASR | ENST00000638421.1 | c.2209G>A | p.Val737Ile | missense_variant | 7/7 | 5 | ENSP00000492190.1 | |||
CASR | ENST00000490131.7 | c.1978G>A | p.Val660Ile | missense_variant | 5/5 | 5 | ENSP00000418685.2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250916Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135696
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461208Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726804
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74334
ClinVar
Submissions by phenotype
Autosomal dominant hypocalcemia 1;C1809471:Familial hypocalciuric hypercalcemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 02, 2023 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 737 of the CASR protein (p.Val737Ile). This variant is present in population databases (rs200318708, gnomAD 0.02%). 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: 572425). 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 | Mar 12, 2022 | - - |
Nephrolithiasis/nephrocalcinosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 02, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at