4-109697626-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001226.4(CASP6):c.226C>T(p.Arg76Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000493 in 1,602,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R76H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001226.4 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 | UniProt |
---|---|---|---|---|---|---|---|
CASP6 | NM_001226.4 | c.226C>T | p.Arg76Cys | missense_variant | 3/7 | ENST00000265164.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASP6 | ENST00000265164.7 | c.226C>T | p.Arg76Cys | missense_variant | 3/7 | 1 | NM_001226.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000624 AC: 15AN: 240242Hom.: 0 AF XY: 0.0000385 AC XY: 5AN XY: 129932
GnomAD4 exome AF: 0.0000503 AC: 73AN: 1450750Hom.: 0 Cov.: 31 AF XY: 0.0000444 AC XY: 32AN XY: 721324
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74326
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 06, 2021 | The c.226C>T (p.R76C) alteration is located in exon 3 (coding exon 3) of the CASP6 gene. This alteration results from a C to T substitution at nucleotide position 226, causing the arginine (R) at amino acid position 76 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at