1-39511832-G-A

Variant names:

• chr1-39511832-G-A
• rs1397794031
• NM_181809.4:c.601G>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_181809.4(BMP8A):​c.601G>A​(p.Ala201Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BMP8A NM_181809.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.35112667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP8A	NM_181809.4	c.601G>A	p.Ala201Thr	missense_variant	Exon 3 of 7	ENST00000331593.6	NP_861525.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP8A	ENST00000331593.6	c.601G>A	p.Ala201Thr	missense_variant	Exon 3 of 7	1	NM_181809.4	ENSP00000327440.5

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1342020 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 672120

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.: 16

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.601G>A (p.A201T) alteration is located in exon 3 (coding exon 3) of the BMP8A gene. This alteration results from a G to A substitution at nucleotide position 601, causing the alanine (A) at amino acid position 201 to be replaced by a threonine (T). 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	0.086
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.093
Sift	Benign	0.073	T
Sift4G	Benign	0.15	T
Polyphen		0.55	P
Vest4		0.17
MutPred		0.41		Loss of sheet (P = 0.302);
MVP		0.71
MPC		2.1
ClinPred		0.94	D
GERP RS		4.5
Varity_R		0.17
gMVP		0.17

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

Other links and lift over

dbSNP: rs1397794031; hg19: chr1-39977504;