rs1181626947
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PP3_StrongPP5_Moderate
The NM_000171.4(GLRA1):c.1246G>A(p.Asp416Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_000171.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLRA1 | NM_000171.4 | c.1246G>A | p.Asp416Asn | missense_variant | 9/9 | ENST00000274576.9 | |
GLRA1 | NM_001146040.2 | c.1270G>A | p.Asp424Asn | missense_variant | 9/9 | ||
GLRA1 | NM_001292000.2 | c.997G>A | p.Asp333Asn | missense_variant | 8/8 | ||
GLRA1 | XM_047417105.1 | c.1294G>A | p.Asp432Asn | missense_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLRA1 | ENST00000274576.9 | c.1246G>A | p.Asp416Asn | missense_variant | 9/9 | 1 | NM_000171.4 | P4 | |
GLRA1 | ENST00000455880.2 | c.1270G>A | p.Asp424Asn | missense_variant | 9/9 | 1 | A1 | ||
GLRA1 | ENST00000462581.6 | c.*1004G>A | 3_prime_UTR_variant, NMD_transcript_variant | 8/8 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251398Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135864
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461640Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727130
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Hyperekplexia 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Neurogenetics Lab, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College | - | The p.Asp424Asn variant in the GLRA1 gene has been detected in a patient with Hyperekplexia. The variant was detected in the homozygous condition in the patient and the same was segregating from the parents. This clearly suggests the autosomal recessive mode of inheritance. The patient was responding to the clonazepam treatment. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at