Variant 17-12763203-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001146312.3(MYOCD):c.2520C>A(p.Ser840Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000851 in 1,614,138 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00086 ( 19 hom. )

Consequence

MYOCD
NM_001146312.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.913

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:

ARHGAP44-AS1 (HGNC:55326): (ARHGAP44 and MYOCD antisense RNA 1)

ARHGAP44-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008124799).

BP6

Variant 17-12763203-C-A is Benign according to our data. Variant chr17-12763203-C-A is described in ClinVar as [Benign]. Clinvar id is 2647495.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 121 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3 linkuse as main transcript	c.2520C>A	p.Ser840Arg	missense_variant	14/14	ENST00000425538.6
ARHGAP44-AS1	NR_104607.1 linkuse as main transcript	n.658G>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6 linkuse as main transcript	c.2520C>A	p.Ser840Arg	missense_variant	14/14	1	NM_001146312.3	P2	Q8IZQ8-3
MYOCD	ENST00000343344.8 linkuse as main transcript	c.2376C>A	p.Ser792Arg	missense_variant	13/13	1		A2	Q8IZQ8-1
MYOCD	ENST00000443061.1 linkuse as main transcript	c.1506C>A	p.Ser502Arg	missense_variant	6/6	1
ARHGAP44-AS1	ENST00000584772.1 linkuse as main transcript	n.616G>T		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.000762

AC:

116

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00694

Gnomad SAS

AF:

0.0129

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00202

AC:

509

AN:

251458

Hom.:

AF XY:

0.00239

AC XY:

325

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00739

Gnomad SAS exome

AF:

0.0115

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.000857

AC:

1253

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

813

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00365

Gnomad4 SAS exome

AF:

0.0110

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00238

GnomAD4 genome

AF:

0.000795

AC:

121

AN:

152254

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00696

Gnomad4 SAS

AF:

0.0127

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.000745

Hom.:

Bravo

AF:

0.000389

ExAC

AF:

0.00203

AC:

247

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

ARHGAP44-AS1: BS1, BS2; MYOCD: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

.;T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.0081

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.81

.;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.091

Sift

Benign

0.061

T;T;T

Sift4G

Benign

0.074

T;T;T

Polyphen

0.050

B;B;.

Vest4

0.14

MutPred

0.21

.;Loss of glycosylation at S792 (P = 0.0102);.;

MVP

0.25

MPC

0.095

ClinPred

0.012

GERP RS

0.22

Varity_R

0.070

gMVP

0.062

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

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