rs782756052
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM5BP4_Moderate
The NM_000169.3(GLA):āc.1175G>Cā(p.Arg392Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,097,078 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R392S) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000169.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLA | NM_000169.3 | c.1175G>C | p.Arg392Thr | missense_variant | 7/7 | ENST00000218516.4 | |
RPL36A-HNRNPH2 | NM_001199973.2 | c.300+2467C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLA | ENST00000218516.4 | c.1175G>C | p.Arg392Thr | missense_variant | 7/7 | 1 | NM_000169.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 exomes AF: 0.0000273 AC: 5AN: 183469Hom.: 0 AF XY: 0.0000147 AC XY: 1AN XY: 67909
GnomAD4 exome AF: 0.00000638 AC: 7AN: 1097078Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1AN XY: 362452
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Fabry disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2022 | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GLA 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. ClinVar contains an entry for this variant (Variation ID: 524212). This variant has not been reported in the literature in individuals affected with GLA-related conditions. This variant is present in population databases (rs782756052, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 392 of the GLA protein (p.Arg392Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at