chr12-55748850-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005811.5(GDF11):​c.710G>C​(p.Ser237Thr) 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GDF11
NM_005811.5 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0
Variant links:
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 rank MANE Protein UniProt
GDF11NM_005811.5 linkc.710G>C p.Ser237Thr missense_variant Exon 2 of 3 ENST00000257868.10 NP_005802.1 O95390A0A024RB20
GDF11XM_006719194.4 linkc.710G>C p.Ser237Thr missense_variant Exon 2 of 4 XP_006719257.1 O95390A0A024RB20

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GDF11ENST00000257868.10 linkc.710G>C p.Ser237Thr missense_variant Exon 2 of 3 1 NM_005811.5 ENSP00000257868.5 O95390
GDF11ENST00000546799.1 linkc.626G>C p.Ser209Thr missense_variant Exon 2 of 4 1 ENSP00000448390.1 H0YI30

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxAug 02, 2024Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Uncertain
0.037
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.39
T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.029
D
MetaRNN
Uncertain
0.47
T
MetaSVM
Benign
-0.60
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.3
N
REVEL
Uncertain
0.32
Sift
Benign
0.13
T
Sift4G
Benign
0.17
T
Polyphen
0.23
B
Vest4
0.57
MutPred
0.56
Gain of catalytic residue at G233 (P = 0.0101);
MVP
0.70
MPC
1.4
ClinPred
0.93
D
GERP RS
4.8
Varity_R
0.30
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: chr12-56142634; API