15-99714829-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_001319206.4(MEF2A):​c.*2058G>T 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 0.00029 (0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High AC in GnomAd4 at 27 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 27 AN: 93436 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.00120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000298

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: 0.0000190

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 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: 0.000289 AC: 27 AN: 93462 Hom.: 0 Cov.: 16 AF XY: 0.000258 AC XY: 11 AN XY: 42576

African (AFR) AF: 0.00120 AC: 24 AN: 20074

American (AMR) AF: 0.000298 AC: 2 AN: 6718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2702

East Asian (EAS) AF: 0.00 AC: 0 AN: 3200

South Asian (SAS) AF: 0.00 AC: 0 AN: 2616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 134

European-Non Finnish (NFE) AF: 0.0000190 AC: 1 AN: 52564

Other (OTH) AF: 0.00 AC: 0 AN: 1196

Alfa AF: 0.00 Hom.: 45

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	0.68
PhyloP100		-0.75

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;