Genetic Variant NM_001365308.1:c.1109C>T (chr7-34078887-C-T) – ACMG Classification: Likely_pathogenic (7 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 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

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.57

Publications

5 publications found

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]

BMPER Gene-Disease associations (from GenCC):

diaphanospondylodysostosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
ischio-vertebral syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BMPER links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 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 VariationId is 30745.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365308.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BMPER	NM_001365308.1	MANE Select	c.1109C>T	p.Pro370Leu	missense	Exon 12 of 15	NP_001352237.1	Q8N8U9
BMPER	NM_133468.5		c.1109C>T	p.Pro370Leu	missense	Exon 13 of 16	NP_597725.1	Q8N8U9
BMPER	NM_001410872.1		c.1079-6869C>T		intron	N/A	NP_001397801.1	A0A3B3ITW7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BMPER	ENST00000649409.2	MANE Select	c.1109C>T	p.Pro370Leu	missense	Exon 12 of 15	ENSP00000497748.1	Q8N8U9
BMPER	ENST00000297161.6	TSL:1	c.1109C>T	p.Pro370Leu	missense	Exon 13 of 16	ENSP00000297161.2	Q8N8U9
BMPER	ENST00000650544.1		c.1004C>T	p.Pro335Leu	missense	Exon 11 of 14	ENSP00000497982.1	A0A3B3ITY4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000653

Hom.:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Diaphanospondylodysostosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

Eigen

Pathogenic

0.98

Eigen_PC

Pathogenic

0.94

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.94

MetaSVM

Uncertain

-0.0023

MutationAssessor

Pathogenic

3.2

PhyloP100

7.6

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-9.3

REVEL

Uncertain

0.64

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.99

MutPred

0.81

Loss of phosphorylation at T374 (P = 0.1071)

MVP

0.92

MPC

0.78

ClinPred

1.0

GERP RS

6.0

Varity_R

0.92

gMVP

0.84

Mutation Taster

=26/74

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over