17-12763404-C-G

Position:

• chr17-12763404-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001146312.3(MYOCD):​c.2721C>G​(p.Gly907Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00464 in 1,605,508 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (160 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (134 hom.)
• Consequence: MYOCD NM_001146312.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.40

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]

ARHGAP44-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-12763404-C-G is Benign according to our data. Variant chr17-12763404-C-G is described in ClinVar as [Benign]. Clinvar id is 780417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOCD	NM_001146312.3	c.2721C>G	p.Gly907Gly	synonymous_variant	14/14	ENST00000425538.6	NP_001139784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOCD	ENST00000425538.6	c.2721C>G	p.Gly907Gly	synonymous_variant	14/14	1	NM_001146312.3	ENSP00000401678.1
MYOCD	ENST00000343344.8	c.2577C>G	p.Gly859Gly	synonymous_variant	13/13	1		ENSP00000341835.4
MYOCD	ENST00000443061.1	c.1707C>G	p.Gly569Gly	synonymous_variant	6/6	1		ENSP00000400148.2
ARHGAP44-AS1	ENST00000584772.1	n.415G>C		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3793 AN: 152086 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00727

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00654 AC: 1604 AN: 245204 Hom.: 58 AF XY: 0.00496 AC XY: 656 AN XY: 132218

Gnomad AFR exome AF: 0.0869

Gnomad AMR exome AF: 0.00449

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000241

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000207

Gnomad OTH exome AF: 0.00201

GnomAD4 exome AF: 0.00251 AC: 3645 AN: 1453304 Hom.: 134 Cov.: 31 AF XY: 0.00221 AC XY: 1592 AN XY: 721814

Gnomad4 AFR exome AF: 0.0850

Gnomad4 AMR exome AF: 0.00482

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000365

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000176

Gnomad4 OTH exome AF: 0.00587

GnomAD4 genome AF: 0.0250 AC: 3812 AN: 152204 Hom.: 160 Cov.: 32 AF XY: 0.0248 AC XY: 1847 AN XY: 74426

Gnomad4 AFR AF: 0.0878

Gnomad4 AMR AF: 0.00726

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0138

Alfa AF: 0.00817 Hom.: 15

Bravo AF: 0.0284

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.49
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs9913758; hg19: chr17-12666721;