ENST00000437473.6:c.-531_-523delCCTCCTCCT

Variant names:

• chr5-88883337-AAGGAGGAGG-A
• rs567979916
• ENST00000437473.6:c.-531_-523delCCTCCTCCT

Variant summary

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

The ENST00000437473.6(MEF2C):​c.-531_-523delCCTCCTCCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 150,194 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEF2C ENST00000437473.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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+4156_-143+4164delCCTCCTCCT		intron	N/A	NP_001180276.1	Q06413-5
	MEF2C	NM_001364329.2		c.-140+4156_-140+4164delCCTCCTCCT		intron	N/A	NP_001351258.1	Q06413-1
	MEF2C	NM_001364330.2		c.-143+4156_-143+4164delCCTCCTCCT		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.-531_-523delCCTCCTCCT		5_prime_UTR	Exon 1 of 11	ENSP00000396219.2	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.-143+4156_-143+4164delCCTCCTCCT		intron	N/A	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000424173.6	TSL:1	c.-143+4156_-143+4164delCCTCCTCCT		intron	N/A	ENSP00000389610.2	Q06413-6

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 150096 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1428 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 916

African (AFR) AF: 0.00 AC: 0 AN: 18

American (AMR) AF: 0.00 AC: 0 AN: 20

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.00 AC: 0 AN: 30

South Asian (SAS) AF: 0.00 AC: 0 AN: 546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 56

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 22

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 674

Other (OTH) AF: 0.00 AC: 0 AN: 56

GnomAD4 genome AF: 0.0000200 AC: 3 AN: 150194 Hom.: 0 Cov.: 27 AF XY: 0.0000136 AC XY: 1 AN XY: 73406

African (AFR) AF: 0.00 AC: 0 AN: 40870

American (AMR) AF: 0.00 AC: 0 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5062

South Asian (SAS) AF: 0.000212 AC: 1 AN: 4716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000297 AC: 2 AN: 67412

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

Alfa AF: 0.0000549 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs567979916; hg19: chr5-88179154;