chr8-144082749-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003801.4(GPAA1):c.19C>T(p.Pro7Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000137 in 1,464,774 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. P7L) has been classified as Uncertain significance.
Frequency
Consequence
NM_003801.4 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 | UniProt |
---|---|---|---|---|---|---|---|
GPAA1 | NM_003801.4 | c.19C>T | p.Pro7Ser | missense_variant | 1/12 | ENST00000355091.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPAA1 | ENST00000355091.9 | c.19C>T | p.Pro7Ser | missense_variant | 1/12 | 1 | NM_003801.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000810 AC: 6AN: 74102Hom.: 0 AF XY: 0.000118 AC XY: 5AN XY: 42486
GnomAD4 exome AF: 0.000147 AC: 193AN: 1312628Hom.: 0 Cov.: 31 AF XY: 0.000138 AC XY: 89AN XY: 645934
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74332
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 28, 2022 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 7 of the GPAA1 protein (p.Pro7Ser). This variant is present in population databases (rs781957928, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GPAA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1514585). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at