chr15-99710725-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001319206.4(MEF2A):​c.1101G>C​(p.Gln367His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

MEF2A
NM_001319206.4 missense

Scores

2
11
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.12
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.756

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MEF2ANM_001319206.4 linkuse as main transcriptc.1101G>C p.Gln367His missense_variant 11/12 ENST00000557942.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MEF2AENST00000557942.6 linkuse as main transcriptc.1101G>C p.Gln367His missense_variant 11/125 NM_001319206.4 Q02078-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsJan 10, 2022The c.1083G>C (p.Q361H) alteration is located in exon 10 (coding exon 8) of the MEF2A gene. This alteration results from a G to C substitution at nucleotide position 1083, causing the glutamine (Q) at amino acid position 361 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
CADD
Benign
23
DANN
Uncertain
1.0
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.91
D;D;D;.;D;D
M_CAP
Benign
0.043
D
MetaRNN
Pathogenic
0.76
D;D;D;D;D;D
MetaSVM
Benign
-0.52
T
MutationTaster
Benign
0.99
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-3.1
D;D;.;D;D;D
REVEL
Uncertain
0.33
Sift
Pathogenic
0.0
D;T;.;D;T;D
Sift4G
Uncertain
0.050
T;D;T;T;D;T
Polyphen
1.0
D;.;D;D;.;D
Vest4
0.74
MVP
0.62
MPC
0.39
ClinPred
0.99
D
GERP RS
2.4
gMVP
0.65

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: chr15-100250930; API