chr7-34078887-C-T

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

Scores

12
5
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.57
Variant links:
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
BMPERNM_001365308.1 linkuse as main transcriptc.1109C>T p.Pro370Leu missense_variant 12/15 ENST00000649409.2 NP_001352237.1
BMPERNM_133468.5 linkuse as main transcriptc.1109C>T p.Pro370Leu missense_variant 13/16 NP_597725.1
BMPERXM_047419939.1 linkuse as main transcriptc.455C>T p.Pro152Leu missense_variant 7/10 XP_047275895.1
BMPERNM_001410872.1 linkuse as main transcriptc.1079-6869C>T intron_variant NP_001397801.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BMPERENST00000649409.2 linkuse as main transcriptc.1109C>T p.Pro370Leu missense_variant 12/15 NM_001365308.1 ENSP00000497748 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
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 providedliterature onlyOMIMOct 08, 2010- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.27
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.36
T;.;T;.
Eigen
Pathogenic
0.98
Eigen_PC
Pathogenic
0.94
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
.;D;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.94
D;D;D;D
MetaSVM
Uncertain
-0.0023
T
MutationAssessor
Pathogenic
3.2
M;.;M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.92
D
PROVEAN
Pathogenic
-9.3
D;.;.;.
REVEL
Uncertain
0.64
Sift
Pathogenic
0.0
D;.;.;.
Sift4G
Uncertain
0.0030
D;.;.;.
Polyphen
1.0
D;.;D;.
Vest4
0.99
MutPred
0.81
Loss of phosphorylation at T374 (P = 0.1071);.;Loss of phosphorylation at T374 (P = 0.1071);.;
MVP
0.92
MPC
0.78
ClinPred
1.0
D
GERP RS
6.0
Varity_R
0.92
gMVP
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs387906993; hg19: chr7-34118499; API