rs607159

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_002397.5(MEF2C):​c.1403C>T​(p.Ser468Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MEF2C
NM_002397.5 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.49
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MEF2C. . Gene score misZ 3.9523 (greater than the threshold 3.09). Trascript score misZ 4.8218 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 20, complex neurodevelopmental disorder.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MEF2CNM_002397.5 linkuse as main transcriptc.1403C>T p.Ser468Phe missense_variant 11/11 ENST00000504921.7
MEF2C-AS2NR_146284.1 linkuse as main transcriptn.256-1G>A splice_acceptor_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MEF2CENST00000504921.7 linkuse as main transcriptc.1403C>T p.Ser468Phe missense_variant 11/111 NM_002397.5 Q06413-1
MEF2C-AS2ENST00000657578.1 linkuse as main transcriptn.232-39374G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1459532
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
725710
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 20 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoFeb 08, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
34
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T;.;.;T;.;.;T;T;.;T;.;.;.;T;T;.;.;.;.
Eigen
Uncertain
0.59
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
.;D;.;D;.;D;.;D;.;D;.;D;.;D;D;D;D;D;D
M_CAP
Benign
0.071
D
MetaRNN
Uncertain
0.55
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.37
T
MutationAssessor
Benign
1.8
L;.;.;.;.;.;L;.;.;.;.;.;.;L;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-1.4
N;N;N;.;.;.;N;.;.;.;.;N;.;.;.;.;.;.;.
REVEL
Uncertain
0.30
Sift
Uncertain
0.0010
D;D;D;.;.;.;D;.;.;.;.;D;.;.;.;.;.;.;.
Sift4G
Uncertain
0.014
D;D;D;.;.;D;D;D;D;D;.;D;D;.;D;D;.;D;D
Polyphen
0.92
P;.;.;.;.;.;P;.;.;.;.;.;D;P;.;D;.;.;.
Vest4
0.49
MutPred
0.31
Loss of phosphorylation at S468 (P = 0.0111);.;.;.;.;.;Loss of phosphorylation at S468 (P = 0.0111);.;.;.;.;.;.;Loss of phosphorylation at S468 (P = 0.0111);.;.;.;.;.;
MVP
0.89
MPC
2.6
ClinPred
0.92
D
GERP RS
5.5
Varity_R
0.42
gMVP
0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs607159; hg19: chr5-88018440; API