Genetic Variant BMP8A:p.Val248Leu (chr1-39521444-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_181809.4(BMP8A):c.742G>T(p.Val248Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/24 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. V248A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 9)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BMP8A
NM_181809.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181809.4. 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
	BMP8A	NM_181809.4	MANE Select	c.742G>T	p.Val248Leu	missense	Exon 4 of 7	NP_861525.2	Q7Z5Y6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP8A	ENST00000331593.6	TSL:1 MANE Select	c.742G>T	p.Val248Leu	missense	Exon 4 of 7	ENSP00000327440.5	Q7Z5Y6
	BMP8A	ENST00000970787.1		c.403G>T	p.Val135Leu	missense	Exon 2 of 5	ENSP00000640846.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

151290

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1133652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

566754

African (AFR)

AF:

0.00

AC:

AN:

28196

American (AMR)

AF:

0.00

AC:

AN:

31888

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21160

East Asian (EAS)

AF:

0.00

AC:

AN:

20012

South Asian (SAS)

AF:

0.00

AC:

AN:

67062

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3810

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

871798

Other (OTH)

AF:

0.00

AC:

AN:

46652

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.098

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.85

M_CAP

Benign

0.012

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.7

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.48

REVEL

Benign

0.087

Sift

Benign

0.14

Sift4G

Benign

0.44

Polyphen

0.0060

Vest4

0.30

MutPred

0.51

Loss of MoRF binding (P = 0.1064)

MVP

0.20

MPC

1.5

ClinPred

0.087

GERP RS

-5.9

Varity_R

0.052

gMVP

0.39

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.27

Position offset: 17

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over