rs318240762
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PM2PP5_Very_StrongBP4
The NM_006129.5(BMP1):c.34G>C(p.Gly12Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 1,564,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. G12G) has been classified as Likely benign.
Frequency
Consequence
NM_006129.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMP1 | NM_006129.5 | c.34G>C | p.Gly12Arg | missense_variant | 1/20 | ENST00000306385.10 | |
BMP1 | NM_001199.4 | c.34G>C | p.Gly12Arg | missense_variant | 1/16 | ENST00000306349.13 | |
BMP1 | NR_033403.2 | n.68G>C | non_coding_transcript_exon_variant | 1/20 | |||
BMP1 | NR_033404.2 | n.68G>C | non_coding_transcript_exon_variant | 1/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMP1 | ENST00000306385.10 | c.34G>C | p.Gly12Arg | missense_variant | 1/20 | 1 | NM_006129.5 | P1 | |
BMP1 | ENST00000306349.13 | c.34G>C | p.Gly12Arg | missense_variant | 1/16 | 1 | NM_001199.4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000108 AC: 2AN: 185424Hom.: 0 AF XY: 0.00000952 AC XY: 1AN XY: 105010
GnomAD4 exome AF: 0.00000566 AC: 8AN: 1412540Hom.: 0 Cov.: 32 AF XY: 0.00000712 AC XY: 5AN XY: 702430
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74430
ClinVar
Submissions by phenotype
not provided Pathogenic:1Other:1
not provided, no classification provided | literature only | UniProtKB/Swiss-Prot | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 17, 2023 | Experimental studies have shown that this missense change affects BMP1 function (PMID: 22482805). For these reasons, this variant has been classified as Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 37307). This missense change has been observed in individuals with osteogenesis imperfecta (PMID: 22482805, 24091809, 29499418). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs318240762, gnomAD 0.002%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 12 of the BMP1 protein (p.Gly12Arg). - |
Osteogenesis imperfecta type 13 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2014 | - - |
Abnormality of the skeletal system Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Kariminejad - Najmabadi Pathology & Genetics Center | Jul 10, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at