dbSNP rs797045703: MEF2C:p.Ala341Pro (chr5-88728572-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000504921.7(MEF2C):c.1021G>C(p.Ala341Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,380,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A341T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

MEF2C
ENST00000504921.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.04

Publications

0 publications found

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 links:

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

MEF2C-AS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29657763).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000504921.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MEF2C	NM_002397.5	MANE Select	c.1021G>C	p.Ala341Pro	missense	Exon 10 of 11	NP_002388.2
MEF2C	NM_001193347.1		c.1051G>C	p.Ala351Pro	missense	Exon 11 of 12	NP_001180276.1
MEF2C	NM_001193350.2		c.1021G>C	p.Ala341Pro	missense	Exon 10 of 11	NP_001180279.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MEF2C	ENST00000504921.7	TSL:1 MANE Select	c.1021G>C	p.Ala341Pro	missense	Exon 10 of 11	ENSP00000421925.5
MEF2C	ENST00000340208.9	TSL:1	c.1051G>C	p.Ala351Pro	missense	Exon 11 of 12	ENSP00000340874.5
MEF2C	ENST00000437473.6	TSL:1	c.1021G>C	p.Ala341Pro	missense	Exon 10 of 11	ENSP00000396219.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1380490

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

680350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31082

American (AMR)

AF:

0.00

AC:

AN:

34820

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24782

East Asian (EAS)

AF:

0.00

AC:

AN:

34998

South Asian (SAS)

AF:

0.00

AC:

AN:

75496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5550

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1068190

Other (OTH)

AF:

0.0000175

AC:

AN:

57088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

0.0015

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.013

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

3.0

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.2

REVEL

Benign

0.21

Sift

Benign

0.25

Sift4G

Benign

0.27

Polyphen

0.82

Vest4

0.64

MutPred

0.35

Gain of disorder (P = 0.0497)

MVP

0.63

MPC

2.7

ClinPred

0.69

GERP RS

5.8

Varity_R

0.32

gMVP

0.64

Mutation Taster

=67/33

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over