chr5-96662496-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001750.7(CAST):c.74A>C(p.Glu25Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000074 in 1,406,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001750.7 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAST | NM_001750.7 | c.74A>C | p.Glu25Ala | missense_variant, splice_region_variant | 1/32 | ENST00000675179.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAST | ENST00000675179.1 | c.74A>C | p.Glu25Ala | missense_variant, splice_region_variant | 1/32 | NM_001750.7 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 151926Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000432 AC: 2AN: 46304Hom.: 0 AF XY: 0.0000725 AC XY: 2AN XY: 27602
GnomAD4 exome AF: 0.0000789 AC: 99AN: 1254396Hom.: 0 Cov.: 34 AF XY: 0.0000844 AC XY: 52AN XY: 615890
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 151926Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4AN XY: 74200
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2022 | This variant has not been reported in the literature in individuals affected with CAST-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 25 of the CAST protein (p.Glu25Ala). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at