17-12666125-G-A

Position:

• chr17-12666125-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001146312.3(MYOCD):​c.-64G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0915 in 1,263,144 control chromosomes in the GnomAD database, including 5,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (568 hom., cov: 32)
  • Exomes 𝑓: 0.093 (5275 hom.)
• Consequence: MYOCD NM_001146312.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.21

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 17-12666125-G-A is Benign according to our data. Variant chr17-12666125-G-A is described in ClinVar as [Benign]. Clinvar id is 1222452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0997 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOCD	NM_001146312.3	c.-64G>A		5_prime_UTR_variant	1/14	ENST00000425538.6	NP_001139784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOCD	ENST00000425538	c.-64G>A		5_prime_UTR_variant	1/14	1	NM_001146312.3	ENSP00000401678.1
MYOCD	ENST00000579237.5	n.-64G>A		non_coding_transcript_exon_variant	1/5	4		ENSP00000462694.1
MYOCD	ENST00000579237.5	n.-64G>A		5_prime_UTR_variant	1/5	4		ENSP00000462694.1

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12449 AN: 152116 Hom.: 569 Cov.: 32

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.0490

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0955

GnomAD4 exome AF: 0.0928 AC: 103080 AN: 1110910 Hom.: 5275 Cov.: 15 AF XY: 0.0921 AC XY: 52344 AN XY: 568480

Gnomad4 AFR exome AF: 0.0532

Gnomad4 AMR exome AF: 0.0525

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.0163

Gnomad4 SAS exome AF: 0.0490

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.0847

GnomAD4 genome AF: 0.0818 AC: 12450 AN: 152234 Hom.: 568 Cov.: 32 AF XY: 0.0808 AC XY: 6017 AN XY: 74428

Gnomad4 AFR AF: 0.0540

Gnomad4 AMR AF: 0.0635

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0178

Gnomad4 SAS AF: 0.0492

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0945

Alfa AF: 0.0807 Hom.: 73

Bravo AF: 0.0782

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs76148496; hg19: chr17-12569442;