17-12686554-A-T

Variant names:

• chr17-12686554-A-T
• rs10491102
• NM_001146312.3:c.56-18574A>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.56-18574A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,190 control chromosomes in the GnomAD database, including 1,002 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 0.11 (1002 hom., cov: 33)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOCD	NM_001146312.3	c.56-18574A>T		intron_variant	Intron 1 of 13	ENST00000425538.6	NP_001139784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOCD	ENST00000425538.6	c.56-18574A>T		intron_variant	Intron 1 of 13	1	NM_001146312.3	ENSP00000401678.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16151 AN: 152072 Hom.: 1001 Cov.: 33

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.0340

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.106 AC: 16168 AN: 152190 Hom.: 1002 Cov.: 33 AF XY: 0.107 AC XY: 7975 AN XY: 74422

African (AFR) AF: 0.0636 AC: 2643 AN: 41528

American (AMR) AF: 0.134 AC: 2050 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3472

East Asian (EAS) AF: 0.0116 AC: 60 AN: 5180

South Asian (SAS) AF: 0.0338 AC: 163 AN: 4826

European-Finnish (FIN) AF: 0.181 AC: 1913 AN: 10586

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8595 AN: 68004

Other (OTH) AF: 0.103 AC: 217 AN: 2112

Alfa AF: 0.113 Hom.: 136

Bravo AF: 0.104

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.66
PhyloP100		0.54
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: rs10491102; hg19: chr17-12589871;