chr15-99674405-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001319206.4(MEF2A):c.403C>T(p.Pro135Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,609,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
MEF2A
NM_001319206.4 missense
NM_001319206.4 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 6.00
Genes affected
MEF2A (HGNC:6993): (myocyte enhancer factor 2A) The protein encoded by this gene is a DNA-binding transcription factor that activates many muscle-specific, growth factor-induced, and stress-induced genes. The encoded protein can act as a homodimer or as a heterodimer and is involved in several cellular processes, including muscle development, neuronal differentiation, cell growth control, and apoptosis. Defects in this gene could be a cause of autosomal dominant coronary artery disease 1 with myocardial infarction (ADCAD1). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.19527656).
BS2
?
High AC in GnomAd at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEF2A | NM_001319206.4 | c.403C>T | p.Pro135Ser | missense_variant | 6/12 | ENST00000557942.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEF2A | ENST00000557942.6 | c.403C>T | p.Pro135Ser | missense_variant | 6/12 | 5 | NM_001319206.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152194Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247772Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134338
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GnomAD4 exome AF: 0.00000892 AC: 13AN: 1457162Hom.: 0 Cov.: 31 AF XY: 0.00000967 AC XY: 7AN XY: 723968
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GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74358
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 21, 2021 | The c.409C>T (p.P137S) alteration is located in exon 6 (coding exon 4) of the MEF2A gene. This alteration results from a C to T substitution at nucleotide position 409, causing the proline (P) at amino acid position 137 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.;.
MutationTaster
Benign
D;D;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;.;B;B;.;B
Vest4
MutPred
Loss of catalytic residue at P136 (P = 0.0117);.;.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at