chr5-88722643-T-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_002397.5(MEF2C):​c.1383A>T​(p.Ser461=) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MEF2C
NM_002397.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.548
Variant links:
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)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 5-88722643-T-A is Benign according to our data. Variant chr5-88722643-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1111815.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.548 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MEF2CNM_002397.5 linkuse as main transcriptc.1383A>T p.Ser461= synonymous_variant 11/11 ENST00000504921.7
MEF2C-AS2NR_146284.1 linkuse as main transcriptn.275T>A non_coding_transcript_exon_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MEF2CENST00000504921.7 linkuse as main transcriptc.1383A>T p.Ser461= synonymous_variant 11/111 NM_002397.5 Q06413-1
MEF2C-AS2ENST00000657578.1 linkuse as main transcriptn.232-39354T>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 20 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 21, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
CADD
Benign
8.4
DANN
Benign
0.78

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: chr5-88018460; API