chr15-99710682-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BS2_Supporting
The NM_001319206.4(MEF2A):c.1058C>T(p.Ser353Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
MEF2A
NM_001319206.4 missense
NM_001319206.4 missense
Scores
4
6
6
Clinical Significance
Conservation
PhyloP100: 7.54
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 Uncertain_significance. Variant got 0 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.772
BS2
High AC in GnomAdExome4 at 14 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEF2A | NM_001319206.4 | c.1058C>T | p.Ser353Leu | missense_variant | 11/12 | ENST00000557942.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEF2A | ENST00000557942.6 | c.1058C>T | p.Ser353Leu | missense_variant | 11/12 | 5 | NM_001319206.4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152248Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249112Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135158
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461338Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 726860
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74384
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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 | Dec 03, 2021 | The c.1040C>T (p.S347L) alteration is located in exon 10 (coding exon 8) of the MEF2A gene. This alteration results from a C to T substitution at nucleotide position 1040, causing the serine (S) at amino acid position 347 to be replaced by a leucine (L). 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
Benign
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;.;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;.;D;D;D
Sift4G
Benign
T;T;T;T;D;T
Polyphen
D;.;D;D;.;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
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