chr7-34078887-C-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_001365308.1(BMPER):c.1109C>T(p.Pro370Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
BMPER
NM_001365308.1 missense
NM_001365308.1 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 7.57
Genes affected
BMPER (HGNC:24154): (BMP binding endothelial regulator) This gene encodes a secreted protein that interacts with, and inhibits bone morphogenetic protein (BMP) function. It has been shown to inhibit BMP2- and BMP4-dependent osteoblast differentiation and BMP-dependent differentiation of the chondrogenic cells. Mutations in this gene are associated with a lethal skeletal disorder, diaphanospondylodysostosis. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.941
PP5
Variant 7-34078887-C-T is Pathogenic according to our data. Variant chr7-34078887-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 30745.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BMPER | NM_001365308.1 | c.1109C>T | p.Pro370Leu | missense_variant | 12/15 | ENST00000649409.2 | NP_001352237.1 | |
BMPER | NM_133468.5 | c.1109C>T | p.Pro370Leu | missense_variant | 13/16 | NP_597725.1 | ||
BMPER | XM_047419939.1 | c.455C>T | p.Pro152Leu | missense_variant | 7/10 | XP_047275895.1 | ||
BMPER | NM_001410872.1 | c.1079-6869C>T | intron_variant | NP_001397801.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BMPER | ENST00000649409.2 | c.1109C>T | p.Pro370Leu | missense_variant | 12/15 | NM_001365308.1 | ENSP00000497748 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Diaphanospondylodysostosis Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 08, 2010 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;.;M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;.;.
REVEL
Uncertain
Sift
Pathogenic
D;.;.;.
Sift4G
Uncertain
D;.;.;.
Polyphen
D;.;D;.
Vest4
MutPred
Loss of phosphorylation at T374 (P = 0.1071);.;Loss of phosphorylation at T374 (P = 0.1071);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at