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GeneBe

6-55774201-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021073.4(BMP5):c.875A>G(p.Gln292Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

BMP5
NM_021073.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59
Variant links:
Genes affected
BMP5 (HGNC:1072): (bone morphogenetic protein 5) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer, which plays a role in bone and cartilage development. Polymorphisms in this gene may be associated with osteoarthritis in human patients. This gene is differentially regulated in multiple human cancers. This gene encodes distinct protein isoforms that may be similarly proteolytically processed. [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20182821).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BMP5NM_021073.4 linkuse as main transcriptc.875A>G p.Gln292Arg missense_variant 4/7 ENST00000370830.4
BMP5NM_001329754.2 linkuse as main transcriptc.875A>G p.Gln292Arg missense_variant 4/6
BMP5NM_001329756.2 linkuse as main transcriptc.875A>G p.Gln292Arg missense_variant 4/5
BMP5XM_011514817.4 linkuse as main transcriptc.875A>G p.Gln292Arg missense_variant 4/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BMP5ENST00000370830.4 linkuse as main transcriptc.875A>G p.Gln292Arg missense_variant 4/71 NM_021073.4 P1P22003-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 22, 2022The c.875A>G (p.Q292R) alteration is located in exon 4 (coding exon 4) of the BMP5 gene. This alteration results from a A to G substitution at nucleotide position 875, causing the glutamine (Q) at amino acid position 292 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
Cadd
Benign
19
Dann
Benign
0.22
DEOGEN2
Benign
0.33
T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.028
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.41
N
MutationTaster
Benign
0.98
N;N
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.65
N
REVEL
Benign
0.077
Sift
Benign
0.95
T
Sift4G
Benign
1.0
T
Polyphen
0.0050
B
Vest4
0.17
MutPred
0.35
Gain of MoRF binding (P = 0.023);
MVP
0.67
MPC
0.22
ClinPred
0.36
T
GERP RS
5.7
Varity_R
0.22
gMVP
0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-55638999; API