Genetic Variant NM_181809.4:c.62G>A (chr1-39492053-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181809.4(BMP8A):c.62G>A(p.Gly21Asp) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 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: 2.21

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14182898).

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.62G>A	p.Gly21Asp	missense	Exon 1 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.62G>A	p.Gly21Asp	missense	Exon 1 of 7	ENSP00000327440.5	Q7Z5Y6
	BMP8A	ENST00000970787.1		c.62G>A	p.Gly21Asp	missense	Exon 1 of 5	ENSP00000640846.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

951574

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

448100

African (AFR)

AF:

0.00

AC:

AN:

18514

American (AMR)

AF:

0.00

AC:

AN:

4424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8654

East Asian (EAS)

AF:

0.00

AC:

AN:

12338

South Asian (SAS)

AF:

0.00

AC:

AN:

18866

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2234

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

839232

Other (OTH)

AF:

0.00

AC:

AN:

34382

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.090

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.35

M_CAP

Pathogenic

0.52

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

PhyloP100

2.2

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.1

REVEL

Benign

0.25

Sift

Benign

0.11

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.23

MutPred

0.31

Loss of glycosylation at P23 (P = 0.1067)

MVP

0.41

MPC

1.8

ClinPred

0.071

GERP RS

0.60

PromoterAI

0.088

Neutral

(source)

Varity_R

0.050

gMVP

0.44

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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