rs751408583
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PVS1_ModeratePP5_ModerateBS2_Supporting
The NM_053274.3(GLMN):c.1720C>T(p.Arg574*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000899 in 1,446,488 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 Likely pathogenic (★).
Frequency
Consequence
NM_053274.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GLMN | ENST00000370360.8 | c.1720C>T | p.Arg574* | stop_gained | Exon 19 of 19 | 1 | NM_053274.3 | ENSP00000359385.3 | ||
GLMN | ENST00000495106.5 | n.*381C>T | non_coding_transcript_exon_variant | Exon 18 of 18 | 1 | ENSP00000436829.1 | ||||
GLMN | ENST00000495106.5 | n.*381C>T | 3_prime_UTR_variant | Exon 18 of 18 | 1 | ENSP00000436829.1 | ||||
GLMN | ENST00000471465.1 | n.666C>T | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250742Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135548
GnomAD4 exome AF: 0.00000899 AC: 13AN: 1446488Hom.: 0 Cov.: 27 AF XY: 0.0000111 AC XY: 8AN XY: 720750
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
The GLMN: p.Arg574Ter variant (rs751408583) was reported in one patient with glomuvenous malformation (Brouillard 2013). This variant is listed in the Genome Aggregation Database (gnomAD) identified on a single chromosome out of 245,592. This variant results in a premature termination codon in the last exon of the GLMN gene. While this may not lead to nonsense-mediated decay, it is expected to create a truncated protein product. Nonsense variants in GLMN are a common mechanism of disease. Based on the above, the p.Arg574Ter variant is considered to be likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at