Variant 1-39511788-C-T 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.557C>T(p.Thr186Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000069 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BMP8A
NM_181809.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

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 link	c.557C>T	p.Thr186Met	missense_variant	3/7	ENST00000331593.6	NP_861525.2	Q7Z5Y6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP8A	ENST00000331593.6 link	c.557C>T	p.Thr186Met	missense_variant	3/7	1	NM_181809.4	ENSP00000327440.5		Q7Z5Y6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

143904

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000747

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000141

Gnomad ASJ

AF:

0.000299

Gnomad EAS

AF:

0.000227

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000463

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000175

AC:

AN:

216862

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

118350

show subpopulations

Gnomad AFR exome

AF:

0.000276

Gnomad AMR exome

AF:

0.000138

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00120

Gnomad SAS exome

AF:

0.0000789

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000819

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000114

AC:

164

AN:

1436748

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

715652

show subpopulations

Gnomad4 AFR exome

AF:

0.0000901

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00188

Gnomad4 SAS exome

AF:

0.000141

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000550

Gnomad4 OTH exome

AF:

0.000151

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000694

AC:

AN:

143996

Hom.:

Cov.:

AF XY:

0.0000574

AC XY:

AN XY:

69640

show subpopulations

Gnomad4 AFR

AF:

0.0000745

Gnomad4 AMR

AF:

0.000141

Gnomad4 ASJ

AF:

0.000299

Gnomad4 EAS

AF:

0.000228

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000463

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000199

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

Sep 04, 2024

The c.557C>T (p.T186M) alteration is located in exon 3 (coding exon 3) of the BMP8A gene. This alteration results from a C to T substitution at nucleotide position 557, causing the threonine (T) at amino acid position 186 to be replaced by a methionine (M). 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

0.082

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.30

Sift

Uncertain

0.020

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.21

MutPred

0.57

Loss of sheet (P = 0.0817);

MVP

0.88

MPC

2.8

ClinPred

0.063

GERP RS

4.5

Varity_R

0.072

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.32

Position offset: -32

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