rs387906993

Positions:

• chr7-34078887-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• 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]

ACMG classification

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	UniProt
BMPER	NM_001365308.1	c.1109C>T	p.Pro370Leu	missense_variant	12/15	ENST00000649409.2
BMPER	NM_133468.5	c.1109C>T	p.Pro370Leu	missense_variant	13/16
BMPER	XM_047419939.1	c.455C>T	p.Pro152Leu	missense_variant	7/10
BMPER	NM_001410872.1	c.1079-6869C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPER	ENST00000649409.2	c.1109C>T	p.Pro370Leu	missense_variant	12/15		NM_001365308.1	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

Submissions by phenotype

Diaphanospondylodysostosis Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 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

Other links and lift over

dbSNP: rs387906993; hg19: chr7-34118499;