chr12-55743735-A-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005811.5(GDF11):āc.419A>Cā(p.Glu140Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000695 in 1,438,772 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 7.0e-7 ( 0 hom. )
Consequence
GDF11
NM_005811.5 missense
NM_005811.5 missense
Scores
2
14
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.09
Genes affected
GDF11 (HGNC:4216): (growth differentiation factor 11) 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 plays a role in the development of the nervous and other organ systems, and may regulate aging. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GDF11 | NM_005811.5 | c.419A>C | p.Glu140Ala | missense_variant | 1/3 | ENST00000257868.10 | |
GDF11 | XM_006719194.4 | c.419A>C | p.Glu140Ala | missense_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GDF11 | ENST00000257868.10 | c.419A>C | p.Glu140Ala | missense_variant | 1/3 | 1 | NM_005811.5 | P1 | |
GDF11 | ENST00000546799.1 | c.338A>C | p.Glu113Ala | missense_variant | 1/4 | 1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 6.95e-7 AC: 1AN: 1438772Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 715758
GnomAD4 exome
AF:
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1
AN:
1438772
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
715758
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at E140 (P = 0.0093);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at