rs372902713
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_020361.5(CPA6):c.290T>C(p.Phe97Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,354 control chromosomes in the GnomAD database, including 1 homozygotes. 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. F97L) has been classified as Uncertain significance.
Frequency
Consequence
NM_020361.5 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 |
---|---|---|---|---|---|---|---|
CPA6 | NM_020361.5 | c.290T>C | p.Phe97Ser | missense_variant | 3/11 | ENST00000297770.10 | |
CPA6 | XM_017013647.2 | c.290T>C | p.Phe97Ser | missense_variant | 3/7 | ||
CPA6 | XM_017013646.2 | c.-127-6295T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPA6 | ENST00000297770.10 | c.290T>C | p.Phe97Ser | missense_variant | 3/11 | 1 | NM_020361.5 | P1 | |
CPA6 | ENST00000518549.1 | n.504T>C | non_coding_transcript_exon_variant | 3/8 | 1 | ||||
CPA6 | ENST00000479862.6 | c.193-6295T>C | intron_variant, NMD_transcript_variant | 1 | |||||
CPA6 | ENST00000638254.1 | c.193-6295T>C | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 249872Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135076
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460152Hom.: 1 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726394
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74354
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 20, 2023 | The c.290T>C (p.F97S) alteration is located in exon 3 (coding exon 3) of the CPA6 gene. This alteration results from a T to C substitution at nucleotide position 290, causing the phenylalanine (F) at amino acid position 97 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Febrile seizures, familial, 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2022 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 574209). This variant has not been reported in the literature in individuals affected with CPA6-related conditions. This variant is present in population databases (rs372902713, gnomAD 0.002%). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 97 of the CPA6 protein (p.Phe97Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at