rs387906992
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001365308.1(BMPER):c.925C>T(p.Gln309Ter) variant causes a stop gained, splice region change. The variant allele was found at a frequency of 0.00000248 in 1,613,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001365308.1 stop_gained, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPER | NM_001365308.1 | c.925C>T | p.Gln309Ter | stop_gained, splice_region_variant | 9/15 | ENST00000649409.2 | |
BMPER | NM_133468.5 | c.925C>T | p.Gln309Ter | stop_gained, splice_region_variant | 10/16 | ||
BMPER | NM_001410872.1 | c.925C>T | p.Gln309Ter | stop_gained, splice_region_variant | 9/14 | ||
BMPER | XM_047419939.1 | c.271C>T | p.Gln91Ter | stop_gained, splice_region_variant | 4/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPER | ENST00000649409.2 | c.925C>T | p.Gln309Ter | stop_gained, splice_region_variant | 9/15 | NM_001365308.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152102Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251318Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135810
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461710Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727162
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74288
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 18, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 30742). This premature translational stop signal has been observed in individual(s) with diaphanospondylodysostosis (PMID: 20869035). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Gln309*) in the BMPER gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BMPER are known to be pathogenic (PMID: 20869035, 21990102). - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 06, 2023 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31589614, 25525159, 20869035) - |
Diaphanospondylodysostosis Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 08, 2010 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at