12-51984099-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP5

The ENST00000257963.9(ACVR1B):​c.912G>A​(p.Met304Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

ACVR1B
ENST00000257963.9 missense

Scores

5
9
5

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 10.0
Variant links:
Genes affected
ACVR1B (HGNC:172): (activin A receptor type 1B) This gene encodes an activin A type IB receptor. Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I and two type II receptors. This protein is a type I receptor which is essential for signaling. Mutations in this gene are associated with pituitary tumors. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jun 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 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), ACVR1B. . Gene score misZ 3.3735 (greater than the threshold 3.09). Trascript score misZ 4.5396 (greater than threshold 3.09). GenCC has associacion of gene with malignant pancreatic neoplasm.
PP5
Variant 12-51984099-G-A is Pathogenic according to our data. Variant chr12-51984099-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1174607.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACVR1BNM_004302.5 linkuse as main transcriptc.912G>A p.Met304Ile missense_variant 5/9 ENST00000257963.9 NP_004293.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACVR1BENST00000257963.9 linkuse as main transcriptc.912G>A p.Met304Ile missense_variant 5/91 NM_004302.5 ENSP00000257963 P1P36896-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Transposition of the great arteries, dextro-looped Pathogenic:1
Pathogenic, no assertion criteria providedcase-controlCytogenetics- Mohapatra Lab, Banaras Hindu UniversityMay 19, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Benign
0.38
T;.;.;.;.
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.96
D;D;D;D;D
M_CAP
Benign
0.029
D
MetaRNN
Uncertain
0.61
D;D;D;D;D
MetaSVM
Benign
-0.53
T
MutationAssessor
Benign
1.0
L;.;L;L;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-3.6
D;D;D;D;D
REVEL
Uncertain
0.51
Sift
Uncertain
0.0050
D;D;D;D;D
Sift4G
Uncertain
0.024
D;D;D;D;D
Polyphen
0.94
P;P;B;P;.
Vest4
0.70
MutPred
0.59
Gain of catalytic residue at L309 (P = 0.0018);.;Gain of catalytic residue at L309 (P = 0.0018);Gain of catalytic residue at L309 (P = 0.0018);.;
MVP
0.95
MPC
1.4
ClinPred
0.97
D
GERP RS
5.3
Varity_R
0.56
gMVP
0.82

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: chr12-52377883; API