Variant 17-12717394-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001146312.3(MYOCD):c.226G>A(p.Asp76Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000784 in 1,613,906 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 6 hom., cov: 31)

Exomes 𝑓: 0.00049 ( 2 hom. )

Consequence

MYOCD
NM_001146312.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.85

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005953878).

BP6

Variant 17-12717394-G-A is Benign according to our data. Variant chr17-12717394-G-A is described in ClinVar as [Benign]. Clinvar id is 768833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 552 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOCD	NM_001146312.3 linkuse as main transcript	c.226G>A	p.Asp76Asn	missense_variant	4/14	ENST00000425538.6	NP_001139784.1	Q8IZQ8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYOCD	ENST00000425538.6 linkuse as main transcript	c.226G>A	p.Asp76Asn	missense_variant	4/14	1	NM_001146312.3	ENSP00000401678.1	Q8IZQ8-3
MYOCD	ENST00000343344.8 linkuse as main transcript	c.226G>A	p.Asp76Asn	missense_variant	4/13	1		ENSP00000341835.4	Q8IZQ8-1
MYOCD	ENST00000579237.5 linkuse as main transcript	n.*144G>A		downstream_gene_variant		4		ENSP00000462694.1	J3KSX3

Frequencies

GnomAD3 genomes

AF:

0.00363

AC:

552

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00118

AC:

296

AN:

251122

Hom.:

AF XY:

0.000847

AC XY:

115

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.0141

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000488

AC:

714

AN:

1461650

Hom.:

Cov.:

AF XY:

0.000433

AC XY:

315

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.0152

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.00363

AC:

552

AN:

152256

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

256

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0126

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000765

Hom.:

Bravo

AF:

0.00432

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00142

AC:

172

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Uncertain

0.43

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.48

T;T

MetaRNN

Benign

0.0060

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.77

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.078

Sift

Benign

0.066

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.0010

B;B

Vest4

0.29

MVP

0.40

MPC

0.073

ClinPred

0.0079

GERP RS

-5.2

Varity_R

0.045

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over