chr5-151822682-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP3
The NM_000171.4(GLRA1):c.1341C>A(p.His447Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,459,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. H447N) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000171.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLRA1 | NM_000171.4 | c.1341C>A | p.His447Gln | missense_variant | 9/9 | ENST00000274576.9 | |
GLRA1 | NM_001146040.2 | c.1365C>A | p.His455Gln | missense_variant | 9/9 | ||
GLRA1 | NM_001292000.2 | c.1092C>A | p.His364Gln | missense_variant | 8/8 | ||
GLRA1 | XM_047417105.1 | c.1389C>A | p.His463Gln | missense_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLRA1 | ENST00000274576.9 | c.1341C>A | p.His447Gln | missense_variant | 9/9 | 1 | NM_000171.4 | P4 | |
GLRA1 | ENST00000455880.2 | c.1365C>A | p.His455Gln | missense_variant | 9/9 | 1 | A1 | ||
GLRA1 | ENST00000462581.6 | c.*1099C>A | 3_prime_UTR_variant, NMD_transcript_variant | 8/8 | 1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251252Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135784
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1459412Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726224
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Hereditary hyperekplexia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 29, 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GLRA1 protein function. This variant has not been reported in the literature in individuals affected with GLRA1-related conditions. This variant is present in population databases (rs773707878, gnomAD 0.003%). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 447 of the GLRA1 protein (p.His447Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at