5-88883309-GAGGAGGAGGAAGA-GAGGAGGAGGAAGAAGGAGGAGGAAGA

Variant names:

• chr5-88883309-G-GAGGAGGAGGAAGA
• rs1164925540
• ENST00000437473.6:c.-507_-495dupTCTTCCTCCTCCT

Variant summary

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

The ENST00000437473.6(MEF2C):​c.-507_-495dupTCTTCCTCCTCCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 151,778 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 27)
• Consequence: MEF2C ENST00000437473.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556
• 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-AS1 (HGNC:48908): (MEF2C antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000437473.6. 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_001193347.1		c.-143+4180_-143+4192dupTCTTCCTCCTCCT		intron	N/A	NP_001180276.1	Q06413-5
	MEF2C	NM_001364329.2		c.-140+4180_-140+4192dupTCTTCCTCCTCCT		intron	N/A	NP_001351258.1	Q06413-1
	MEF2C	NM_001364330.2		c.-143+4180_-143+4192dupTCTTCCTCCTCCT		intron	N/A	NP_001351259.1	Q06413-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	ENST00000437473.6	TSL:1	c.-507_-495dupTCTTCCTCCTCCT		5_prime_UTR	Exon 1 of 11	ENSP00000396219.2	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.-143+4180_-143+4192dupTCTTCCTCCTCCT		intron	N/A	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000424173.6	TSL:1	c.-143+4180_-143+4192dupTCTTCCTCCTCCT		intron	N/A	ENSP00000389610.2	Q06413-6

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151778 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151778 Hom.: 0 Cov.: 27 AF XY: 0.0000135 AC XY: 1 AN XY: 74122

African (AFR) AF: 0.0000726 AC: 3 AN: 41330

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67932

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1164925540; hg19: chr5-88179126;