chr10-86923499-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_004329.3(BMPR1A):​c.1466G>A​(p.Ser489Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S489T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

BMPR1A
NM_004329.3 missense

Scores

3
4
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 10.0
Variant links:
Genes affected
BMPR1A (HGNC:1076): (bone morphogenetic protein receptor type 1A) The bone morphogenetic protein (BMP) receptors are a family of transmembrane serine/threonine kinases that include the type I receptors BMPR1A and BMPR1B and the type II receptor BMPR2. These receptors are also closely related to the activin receptors, ACVR1 and ACVR2. The ligands of these receptors are members of the TGF-beta superfamily. TGF-betas and activins transduce their signals through the formation of heteromeric complexes with 2 different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors require their respective type II receptors for ligand binding. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), BMPR1A. . Gene score misZ 1.9176 (greater than the threshold 3.09). Trascript score misZ 3.8989 (greater than threshold 3.09). GenCC has associacion of gene with polyposis syndrome, hereditary mixed, 2, generalized juvenile polyposis/juvenile polyposis coli, hereditary mixed polyposis syndrome, pulmonary arterial hypertension, juvenile polyposis syndrome.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BMPR1ANM_004329.3 linkuse as main transcriptc.1466G>A p.Ser489Asn missense_variant 12/13 ENST00000372037.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BMPR1AENST00000372037.8 linkuse as main transcriptc.1466G>A p.Ser489Asn missense_variant 12/131 NM_004329.3 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.84e-7
AC:
1
AN:
1461892
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727246
show subpopulations
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.059
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.57
D
Eigen
Uncertain
0.67
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
1.0
D
M_CAP
Benign
0.047
D
MetaRNN
Uncertain
0.55
D
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
0.99
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.28
Sift
Benign
0.066
T
Sift4G
Benign
0.095
T
Polyphen
0.92
P
Vest4
0.64
MutPred
0.38
Loss of MoRF binding (P = 0.1138);
MVP
0.55
MPC
1.5
ClinPred
0.91
D
GERP RS
5.7
Varity_R
0.50
gMVP
0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-88683256; API