MEF2A p.Thr200Ser

Variant names:

• chr15-99674600-A-T
• NM_001319206.4:c.598A>T
• MEF2A p.Thr200Ser

Your query was ambiguous. Multiple possible variants found:

• chr15-99674600-A-T
• chr15-99674601-C-G
• chr15-99674600-ACT-TCC
• chr15-99674600-ACT-TCA
• chr15-99674600-ACT-TCG
• chr15-99674601-CT-GC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001319206.4(MEF2A):​c.598A>T​(p.Thr200Ser) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T200N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEF2A NM_001319206.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.111757755).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319206.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2A	NM_001319206.4	MANE Select	c.598A>T	p.Thr200Ser	missense	Exon 6 of 12	NP_001306135.1	Q02078-2
	MEF2A	NM_001400028.1		c.736A>T	p.Thr246Ser	missense	Exon 7 of 12	NP_001386957.1
	MEF2A	NM_001365201.3		c.616A>T	p.Thr206Ser	missense	Exon 6 of 12	NP_001352130.1	A0A8I5KVQ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2A	ENST00000557942.6	TSL:5 MANE Select	c.598A>T	p.Thr200Ser	missense	Exon 6 of 12	ENSP00000453095.1	Q02078-2
	MEF2A	ENST00000354410.9	TSL:1	c.604A>T	p.Thr202Ser	missense	Exon 6 of 11	ENSP00000346389.5	Q02078-5
	MEF2A	ENST00000947006.1		c.736A>T	p.Thr246Ser	missense	Exon 6 of 12	ENSP00000617065.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Benign	0.91
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.28
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.29
Sift	Benign	0.42	T
Sift4G	Benign	0.32	T
gMVP		0.20

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-100214805;