17-12760999-CTTCT-C

Position:

• chr17-12760999-CTTCT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001146312.3(MYOCD):​c.2389+297_2389+300delTTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 300,256 control chromosomes in the GnomAD database, including 12,249 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (5414 hom., cov: 24)
  • Exomes 𝑓: 0.29 (6835 hom.)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.865

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 -10 ACMG points.

• BP6: Variant 17-12760999-CTTCT-C is Benign according to our data. Variant chr17-12760999-CTTCT-C is described in ClinVar as [Benign]. Clinvar id is 1269164.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOCD	NM_001146312.3	c.2389+297_2389+300delTTCT		intron_variant		ENST00000425538.6	NP_001139784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOCD	ENST00000425538.6	c.2389+297_2389+300delTTCT		intron_variant		1	NM_001146312.3	ENSP00000401678.1
MYOCD	ENST00000343344.8	c.2245+297_2245+300delTTCT		intron_variant		1		ENSP00000341835.4
MYOCD	ENST00000443061.1	c.1375+297_1375+300delTTCT		intron_variant		1		ENSP00000400148.2
ARHGAP44-AS1	ENST00000584772.1	n.2816_2819delAGAA		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36684 AN: 151866 Hom.: 5408 Cov.: 24

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.253

GnomAD4 exome AF: 0.287 AC: 42520 AN: 148272 Hom.: 6835 AF XY: 0.286 AC XY: 21754 AN XY: 76024

Gnomad4 AFR exome AF: 0.0781

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.367

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.241 AC: 36703 AN: 151984 Hom.: 5414 Cov.: 24 AF XY: 0.244 AC XY: 18139 AN XY: 74276

Gnomad4 AFR AF: 0.0783

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.249

Alfa AF: 0.280 Hom.: 767

Bravo AF: 0.225

Asia WGS AF: 0.295 AC: 1027 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs58627748; hg19: chr17-12664316;