NM_001146312.3:c.122-1135A>G

Variant names:

• chr17-12714384-A-G
• rs1714984
• NM_001146312.3:c.122-1135A>G

Variant summary

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

The NM_001146312.3(MYOCD):​c.122-1135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 149,964 control chromosomes in the GnomAD database, including 34,130 homozygotes. 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 0.65 (34130 hom., cov: 27)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• Publications: 12 publications found

Genes affected

MYOCD (HGNC:16067): (myocardin) This gene encodes a nuclear protein, which is expressed in heart, aorta, and in smooth muscle cell-containing tissues. It functions as a transcriptional co-activator of serum response factor (SRF) and modulates expression of cardiac and smooth muscle-specific SRF-target genes, and thus may play a crucial role in cardiogenesis and differentiation of the smooth muscle cell lineage. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

MYOCD-AS1 (HGNC:40750): (MYOCD antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146312.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOCD	NM_001146312.3	MANE Select	c.122-1135A>G		intron	N/A	NP_001139784.1
	MYOCD	NM_153604.4		c.122-1135A>G		intron	N/A	NP_705832.1
	MYOCD	NM_001378306.1		c.-116-1135A>G		intron	N/A	NP_001365235.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOCD	ENST00000425538.6	TSL:1 MANE Select	c.122-1135A>G		intron	N/A	ENSP00000401678.1
	MYOCD	ENST00000343344.8	TSL:1	c.122-1135A>G		intron	N/A	ENSP00000341835.4
	MYOCD	ENST00000579237.5	TSL:4	n.*40-1135A>G		intron	N/A	ENSP00000462694.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 96985 AN: 149846 Hom.: 34137 Cov.: 27

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.667

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.647 AC: 96987 AN: 149964 Hom.: 34130 Cov.: 27 AF XY: 0.650 AC XY: 47524 AN XY: 73074

African (AFR) AF: 0.343 AC: 13959 AN: 40644

American (AMR) AF: 0.688 AC: 10386 AN: 15088

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2835 AN: 3468

East Asian (EAS) AF: 0.691 AC: 3485 AN: 5046

South Asian (SAS) AF: 0.618 AC: 2923 AN: 4728

European-Finnish (FIN) AF: 0.820 AC: 8268 AN: 10082

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.782 AC: 52866 AN: 67632

Other (OTH) AF: 0.666 AC: 1387 AN: 2084

Alfa AF: 0.710 Hom.: 60871

Bravo AF: 0.625

Asia WGS AF: 0.605 AC: 2105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.1
DANN	Benign	0.75
PhyloP100		-0.30
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: rs1714984; hg19: chr17-12617701;