1-39522412-G-T

Variant summary

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

The NM_181809.4(BMP8A):​c.878G>T​(p.Arg293Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R293H) has been classified as Benign.

Frequency

Genomes: not found (cov: 28)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

BMP8A
NM_181809.4 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0210
Variant links:
Genes affected
BMP8A (HGNC:21650): (bone morphogenetic protein 8a) 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. This protein may play a role in development of the reproductive system. This gene may have arose from a gene duplication event and its gene duplicate is also present on chromosome 1. [provided by RefSeq, Jul 2016]
PPIEL (HGNC:33195): (peptidylprolyl isomerase E like (pseudogene)) This transcribed pseudogene is related to PPIE (Gene ID: 10450). Expression of this pseudogene may be downregulated in non-small cell lung cancer (NSCLC). Differential DNA methylation of this locus may be associated with intellectual disability and bipolar disorder in human patients. [provided by RefSeq, Sep 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=0.1916416).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BMP8ANM_181809.4 linkc.878G>T p.Arg293Leu missense_variant Exon 5 of 7 ENST00000331593.6 NP_861525.2 Q7Z5Y6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BMP8AENST00000331593.6 linkc.878G>T p.Arg293Leu missense_variant Exon 5 of 7 1 NM_181809.4 ENSP00000327440.5 Q7Z5Y6

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1418392
Hom.:
0
Cov.:
43
AF XY:
0.00
AC XY:
0
AN XY:
704492
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
14
DANN
Uncertain
0.98
DEOGEN2
Benign
0.19
T
Eigen
Benign
-0.94
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.20
T
M_CAP
Benign
0.077
D
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.69
N
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-2.5
D
REVEL
Benign
0.13
Sift
Benign
0.062
T
Sift4G
Benign
0.29
T
Polyphen
0.30
B
Vest4
0.29
MutPred
0.47
Loss of disorder (P = 0.0457);
MVP
0.55
MPC
1.8
ClinPred
0.19
T
GERP RS
3.3
Varity_R
0.099
gMVP
0.39

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: rs6525; hg19: chr1-39988084; API