chr17-12747460-C-T

Variant names:

• chr17-12747460-C-T
• rs1984661
• NM_001146312.3:c.1125+1388C>T

Variant summary

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

The NM_001146312.3(MYOCD):​c.1125+1388C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,776 control chromosomes in the GnomAD database, including 23,439 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 0.55 (23439 hom., cov: 30)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 5 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 Gene-Disease associations (from GenCC):

• megabladder, congenital

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOCD	NM_001146312.3	MANE Select	c.1125+1388C>T		intron	N/A	NP_001139784.1	Q8IZQ8-3
	MYOCD	NM_153604.4		c.1125+1388C>T		intron	N/A	NP_705832.1	Q8IZQ8-1
	MYOCD	NM_001378306.1		c.888+1388C>T		intron	N/A	NP_001365235.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOCD	ENST00000425538.6	TSL:1 MANE Select	c.1125+1388C>T		intron	N/A	ENSP00000401678.1	Q8IZQ8-3
	MYOCD	ENST00000343344.8	TSL:1	c.1125+1388C>T		intron	N/A	ENSP00000341835.4	Q8IZQ8-1
	MYOCD	ENST00000443061.1	TSL:1	c.240+1388C>T		intron	N/A	ENSP00000400148.2	Q6N065

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83531 AN: 151658 Hom.: 23437 Cov.: 30

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.551 AC: 83557 AN: 151776 Hom.: 23439 Cov.: 30 AF XY: 0.559 AC XY: 41426 AN XY: 74168

African (AFR) AF: 0.437 AC: 18085 AN: 41344

American (AMR) AF: 0.608 AC: 9264 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1726 AN: 3470

East Asian (EAS) AF: 0.695 AC: 3574 AN: 5140

South Asian (SAS) AF: 0.629 AC: 3022 AN: 4804

European-Finnish (FIN) AF: 0.651 AC: 6853 AN: 10534

Middle Eastern (MID) AF: 0.514 AC: 147 AN: 286

European-Non Finnish (NFE) AF: 0.577 AC: 39233 AN: 67944

Other (OTH) AF: 0.545 AC: 1143 AN: 2098

Alfa AF: 0.570 Hom.: 16090

Bravo AF: 0.538

Asia WGS AF: 0.662 AC: 2302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.97
DANN	Benign	0.52
PhyloP100		-0.37
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: rs1984661; hg19: chr17-12650777;