chr17-12734054-T-G

Variant names:

• chr17-12734054-T-G
• rs9905820
• NM_001146312.3:c.416-2107T>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.416-2107T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,644 control chromosomes in the GnomAD database, including 15,748 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 0.45 (15748 hom., cov: 30)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 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.416-2107T>G		intron	N/A	NP_001139784.1	Q8IZQ8-3
	MYOCD	NM_153604.4		c.416-2107T>G		intron	N/A	NP_705832.1	Q8IZQ8-1
	MYOCD	NM_001378306.1		c.179-2107T>G		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.416-2107T>G		intron	N/A	ENSP00000401678.1	Q8IZQ8-3
	MYOCD	ENST00000343344.8	TSL:1	c.416-2107T>G		intron	N/A	ENSP00000341835.4	Q8IZQ8-1
	MYOCD	ENST00000860866.1		c.416-2107T>G		intron	N/A	ENSP00000530925.1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68279 AN: 151526 Hom.: 15725 Cov.: 30

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.451 AC: 68344 AN: 151644 Hom.: 15748 Cov.: 30 AF XY: 0.454 AC XY: 33631 AN XY: 74060

African (AFR) AF: 0.516 AC: 21302 AN: 41310

American (AMR) AF: 0.458 AC: 6974 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1206 AN: 3466

East Asian (EAS) AF: 0.670 AC: 3430 AN: 5120

South Asian (SAS) AF: 0.482 AC: 2313 AN: 4802

European-Finnish (FIN) AF: 0.473 AC: 4946 AN: 10462

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26811 AN: 67926

Other (OTH) AF: 0.411 AC: 867 AN: 2112

Alfa AF: 0.420 Hom.: 26947

Bravo AF: 0.455

Asia WGS AF: 0.544 AC: 1892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.67
PhyloP100		-0.0060
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: rs9905820; hg19: chr17-12637371; COSMIC: COSV58500262;