1-156477106-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005920.4(MEF2D):​c.761C>T​(p.Pro254Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MEF2D
NM_005920.4 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.64
Variant links:
Genes affected
MEF2D (HGNC:6997): (myocyte enhancer factor 2D) This gene is a member of the myocyte-specific enhancer factor 2 (MEF2) family of transcription factors. Members of this family are involved in control of muscle and neuronal cell differentiation and development, and are regulated by class II histone deacetylases. Fusions of the encoded protein with Deleted in Azoospermia-Associated Protein 1 (DAZAP1) due to a translocation have been found in an acute lymphoblastic leukemia cell line, suggesting a role in leukemogenesis. The encoded protein may also be involved in Parkinson disease and myotonic dystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MEF2DNM_005920.4 linkc.761C>T p.Pro254Leu missense_variant Exon 7 of 12 ENST00000348159.9 NP_005911.1 Q14814-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MEF2DENST00000348159.9 linkc.761C>T p.Pro254Leu missense_variant Exon 7 of 12 1 NM_005920.4 ENSP00000271555.5 Q14814-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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
AF:
0.0000116
AC:
17
AN:
1461748
Hom.:
0
Cov.:
30
AF XY:
0.0000110
AC XY:
8
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.00000756
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 17, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.761C>T (p.P254L) alteration is located in exon 7 (coding exon 6) of the MEF2D gene. This alteration results from a C to T substitution at nucleotide position 761, causing the proline (P) at amino acid position 254 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.092
T
BayesDel_noAF
Benign
-0.37
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.53
.;D;.
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.035
D
MetaRNN
Uncertain
0.50
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.2
.;L;L
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-6.6
.;D;D
REVEL
Benign
0.21
Sift
Benign
0.036
.;D;D
Sift4G
Uncertain
0.046
D;D;D
Polyphen
0.86, 0.088
.;P;B
Vest4
0.66
MutPred
0.27
.;Loss of glycosylation at P254 (P = 0.0016);Loss of glycosylation at P254 (P = 0.0016);
MVP
0.19
MPC
0.67
ClinPred
1.0
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.45
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs867321500; hg19: chr1-156446898; API