1-156477091-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005920.4(MEF2D):​c.776C>G​(p.Thr259Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MEF2D
NM_005920.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07936156).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MEF2DNM_005920.4 linkc.776C>G p.Thr259Ser 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.776C>G p.Thr259Ser missense_variant Exon 7 of 12 1 NM_005920.4 ENSP00000271555.5 Q14814-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.776C>G (p.T259S) alteration is located in exon 7 (coding exon 6) of the MEF2D gene. This alteration results from a C to G substitution at nucleotide position 776, causing the threonine (T) at amino acid position 259 to be replaced by a serine (S). 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
0.064
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
21
DANN
Benign
0.85
DEOGEN2
Benign
0.081
.;T;.
Eigen
Benign
-0.19
Eigen_PC
Benign
0.048
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.63
T;T;T
M_CAP
Benign
0.0028
T
MetaRNN
Benign
0.079
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
.;N;N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.070
.;N;N
REVEL
Benign
0.045
Sift
Benign
0.91
.;T;T
Sift4G
Benign
0.79
T;T;T
Polyphen
0.0, 0.0020
.;B;B
Vest4
0.12
MutPred
0.15
.;Loss of glycosylation at S258 (P = 0.0546);Loss of glycosylation at S258 (P = 0.0546);
MVP
0.32
MPC
0.29
ClinPred
0.53
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.17
gMVP
0.19

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: rs1671665247; hg19: chr1-156446883; API