NM_002397.5:c.1207A>T

Variant names:

• chr5-88722819-T-A
• rs753002290
• NM_002397.5:c.1207A>T

Variant summary

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

The NM_002397.5(MEF2C):​c.1207A>T​(p.Thr403Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T403A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEF2C NM_002397.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94
• Publications: 0 publications found

Genes affected

MEF2C (HGNC:6996): (myocyte enhancer factor 2C) This locus encodes a member of the MADS box transcription enhancer factor 2 (MEF2) family of proteins, which play a role in myogenesis. The encoded protein, MEF2 polypeptide C, has both trans-activating and DNA binding activities. This protein may play a role in maintaining the differentiated state of muscle cells. Mutations and deletions at this locus have been associated with severe cognitive disability, stereotypic movements, epilepsy, and cerebral malformation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2010]

MEF2C-AS2 (HGNC:53115): (MEF2C antisense RNA 2)

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=0.17943758).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002397.5. 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
	MEF2C	NM_002397.5	MANE Select	c.1207A>T	p.Thr403Ser	missense	Exon 11 of 11	NP_002388.2
	MEF2C	NM_001193347.1		c.1237A>T	p.Thr413Ser	missense	Exon 12 of 12	NP_001180276.1	Q06413-5
	MEF2C	NM_001193350.2		c.1207A>T	p.Thr403Ser	missense	Exon 11 of 11	NP_001180279.1	Q06413-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	ENST00000504921.7	TSL:1 MANE Select	c.1207A>T	p.Thr403Ser	missense	Exon 11 of 11	ENSP00000421925.5	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.1237A>T	p.Thr413Ser	missense	Exon 12 of 12	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000437473.6	TSL:1	c.1207A>T	p.Thr403Ser	missense	Exon 11 of 11	ENSP00000396219.2	Q06413-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.92
Eigen	Benign	-0.12
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.18	T
PhyloP100		3.9
Sift4G	Benign	0.47	T
MVP		0.24
ClinPred		0.76	D
GERP RS		5.4
Varity_R		0.17
Mutation Taster		=52/48	polymorphism

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

Other links and lift over

dbSNP: rs753002290; hg19: chr5-88018636;