rs1554300601

Variant names:

• chr7-33970336-T-A
• rs1554300601
• NM_001365308.1:c.410T>A
• BMPER p.Val137Asp

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3 PP5

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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V137I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BMPER NM_001365308.1 missense
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 5.50
• Publications: 3 publications found

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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• ischio-vertebral syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 Pathogenic/Likely_pathogenic. ClinVar VariationId is 559441.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPER	NM_001365308.1	MANE Select	c.410T>A	p.Val137Asp	missense	Exon 5 of 15	NP_001352237.1	Q8N8U9
	BMPER	NM_133468.5		c.410T>A	p.Val137Asp	missense	Exon 6 of 16	NP_597725.1	Q8N8U9
	BMPER	NM_001410872.1		c.410T>A	p.Val137Asp	missense	Exon 5 of 14	NP_001397801.1	A0A3B3ITW7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPER	ENST00000649409.2	MANE Select	c.410T>A	p.Val137Asp	missense	Exon 5 of 15	ENSP00000497748.1	Q8N8U9
	BMPER	ENST00000297161.6	TSL:1	c.410T>A	p.Val137Asp	missense	Exon 6 of 16	ENSP00000297161.2	Q8N8U9
	BMPER	ENST00000650544.1		c.410T>A	p.Val137Asp	missense	Exon 5 of 14	ENSP00000497982.1	A0A3B3ITY4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic/Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
2	-	-	Diaphanospondylodysostosis (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	26
DANN	Benign	0.97
DEOGEN2	Uncertain	0.50	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Varity_R		0.91
gMVP		0.77
Mutation Taster		=6/94	disease causing (ClinVar)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1554300601;

hg19: chr7-34009948;