Variant chr17-12763420-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001146312.3(MYOCD):c.2737C>A(p.Gln913Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q913Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MYOCD
NM_001146312.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.12

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16463298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3 linkuse as main transcript	c.2737C>A	p.Gln913Lys	missense_variant	14/14	ENST00000425538.6
ARHGAP44-AS1	NR_104607.1 linkuse as main transcript	n.441G>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.2737C>A	p.Gln913Lys	missense_variant	14/14	1	NM_001146312.3	P2	Q8IZQ8-3
MYOCD	ENST00000343344.8 linkuse as main transcript	c.2593C>A	p.Gln865Lys	missense_variant	13/13	1		A2	Q8IZQ8-1
MYOCD	ENST00000443061.1 linkuse as main transcript	c.1723C>A	p.Gln575Lys	missense_variant	6/6	1
ARHGAP44-AS1	ENST00000584772.1 linkuse as main transcript	n.399G>T		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459038

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725484

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2023

The c.2737C>A (p.Q913K) alteration is located in exon 14 (coding exon 14) of the MYOCD gene. This alteration results from a C to A substitution at nucleotide position 2737, causing the glutamine (Q) at amino acid position 913 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.34

.;T;T

Eigen

Benign

0.046

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.91

N;N;N

REVEL

Benign

0.052

Sift

Uncertain

0.022

D;D;T

Sift4G

Uncertain

0.056

T;T;T

Polyphen

0.21

B;B;.

Vest4

0.16

MutPred

0.20

.;Gain of ubiquitination at Q865 (P = 0.006);.;

MVP

0.28

MPC

0.12

ClinPred

0.43

GERP RS

6.1

Varity_R

0.19

gMVP

0.16

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over