NM_001319206.4:c.*2058G>C

Variant names:

• chr15-99714829-G-C
• rs1059759
• NM_001319206.4:c.*2058G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001319206.4(MEF2A):​c.*2058G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (638 hom., cov: 16)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEF2A NM_001319206.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753
• Publications: 6 publications found

Genes affected

MEF2A (HGNC:6993): (myocyte enhancer factor 2A) The protein encoded by this gene is a DNA-binding transcription factor that activates many muscle-specific, growth factor-induced, and stress-induced genes. The encoded protein can act as a homodimer or as a heterodimer and is involved in several cellular processes, including muscle development, neuronal differentiation, cell growth control, and apoptosis. Defects in this gene could be a cause of autosomal dominant coronary artery disease 1 with myocardial infarction (ADCAD1). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4	c.*2058G>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000557942.6	NP_001306135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2A	ENST00000557942.6	c.*2058G>C		3_prime_UTR_variant	Exon 12 of 12	5	NM_001319206.4	ENSP00000453095.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 12145 AN: 93094 Hom.: 637 Cov.: 16

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.0447

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.153

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.131 AC: 12155 AN: 93118 Hom.: 638 Cov.: 16 AF XY: 0.133 AC XY: 5643 AN XY: 42414

African (AFR) AF: 0.0868 AC: 1740 AN: 20036

American (AMR) AF: 0.147 AC: 987 AN: 6692

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 411 AN: 2692

East Asian (EAS) AF: 0.212 AC: 673 AN: 3176

South Asian (SAS) AF: 0.153 AC: 397 AN: 2596

European-Finnish (FIN) AF: 0.138 AC: 483 AN: 3502

Middle Eastern (MID) AF: 0.366 AC: 49 AN: 134

European-Non Finnish (NFE) AF: 0.137 AC: 7194 AN: 52360

Other (OTH) AF: 0.158 AC: 188 AN: 1192

Alfa AF: 0.0337 Hom.: 45

Bravo AF: 0.100

Asia WGS AF: 0.138 AC: 468 AN: 3400

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.67
PhyloP100		-0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1059759; hg19: chr15-100255034;