7-33970336-T-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_001365308.1(BMPER):c.410T>A(p.Val137Asp) variant causes a missense change. 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 Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
BMPER
NM_001365308.1 missense
NM_001365308.1 missense
Scores
7
8
3
Clinical Significance
Conservation
PhyloP100: 5.50
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.796
PP5
Variant 7-33970336-T-A is Pathogenic according to our data. Variant chr7-33970336-T-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 559441.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPER | NM_001365308.1 | c.410T>A | p.Val137Asp | missense_variant | 5/15 | ENST00000649409.2 | |
BMPER | NM_133468.5 | c.410T>A | p.Val137Asp | missense_variant | 6/16 | ||
BMPER | NM_001410872.1 | c.410T>A | p.Val137Asp | missense_variant | 5/14 | ||
BMPER | XM_047419939.1 | c.-145T>A | 5_prime_UTR_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPER | ENST00000649409.2 | c.410T>A | p.Val137Asp | missense_variant | 5/15 | NM_001365308.1 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Diaphanospondylodysostosis Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 26, 2019 | - - |
Likely pathogenic, no assertion criteria provided | clinical testing | The Danek Gertner Institute of Human Genetics, Sheba Medical Center | Apr 15, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Benign
DEOGEN2
Uncertain
T;.;T;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;.;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.;.;.;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;.;.;.;.;.
Sift4G
Pathogenic
D;.;.;.;.;.;.
Polyphen
D;.;D;.;.;.;.
Vest4
MutPred
Loss of catalytic residue at V137 (P = 0.004);Loss of catalytic residue at V137 (P = 0.004);Loss of catalytic residue at V137 (P = 0.004);Loss of catalytic residue at V137 (P = 0.004);Loss of catalytic residue at V137 (P = 0.004);Loss of catalytic residue at V137 (P = 0.004);.;
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