Variant chr1-39511252-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_181809.4(BMP8A):c.413G>A(p.Gly138Glu) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00090 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

BMP8A
NM_181809.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.10

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]

BMP8A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP8A	NM_181809.4 linkuse as main transcript	c.413G>A	p.Gly138Glu	missense_variant	2/7	ENST00000331593.6	NP_861525.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP8A	ENST00000331593.6 linkuse as main transcript	c.413G>A	p.Gly138Glu	missense_variant	2/7	1	NM_181809.4	ENSP00000327440	P1

Frequencies

GnomAD3 genomes

AF:

0.000711

AC:

104

AN:

146312

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000896

Gnomad ASJ

AF:

0.000291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000302

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.00154

GnomAD3 exomes

AF:

0.000354

AC:

AN:

93126

Hom.:

AF XY:

0.000316

AC XY:

AN XY:

47540

show subpopulations

Gnomad AFR exome

AF:

0.000155

Gnomad AMR exome

AF:

0.000199

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000864

Gnomad NFE exome

AF:

0.000801

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000904

AC:

1115

AN:

1234006

Hom.:

Cov.:

AF XY:

0.000902

AC XY:

551

AN XY:

611136

show subpopulations

Gnomad4 AFR exome

AF:

0.000143

Gnomad4 AMR exome

AF:

0.000373

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000551

Gnomad4 NFE exome

AF:

0.00110

Gnomad4 OTH exome

AF:

0.000620

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000711

AC:

104

AN:

146312

Hom.:

Cov.:

AF XY:

0.000691

AC XY:

AN XY:

70958

show subpopulations

Gnomad4 AFR

AF:

0.000127

Gnomad4 AMR

AF:

0.000896

Gnomad4 ASJ

AF:

0.000291

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000302

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.00154

Alfa

AF:

0.00135

Hom.:

ExAC

AF:

0.000418

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 05, 2022

The c.413G>A (p.G138E) alteration is located in exon 2 (coding exon 2) of the BMP8A gene. This alteration results from a G to A substitution at nucleotide position 413, causing the glycine (G) at amino acid position 138 to be replaced by a glutamic acid (E). 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

0.23

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.32

MetaRNN

Uncertain

0.57

MetaSVM

Uncertain

-0.26

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-6.2

REVEL

Uncertain

0.45

Sift

Benign

0.093

Sift4G

Benign

0.093

Polyphen

1.0

Vest4

0.59

MVP

0.86

MPC

3.2

ClinPred

0.20

GERP RS

4.3

Varity_R

0.53

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over