17-12763087-G-C

Position:

• chr17-12763087-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001146312.3(MYOCD):​c.2404G>C​(p.Ala802Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYOCD NM_001146312.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOCD	NM_001146312.3	c.2404G>C	p.Ala802Pro	missense_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.2404G>C	p.Ala802Pro	missense_variant	14/14	1	NM_001146312.3	ENSP00000401678.1
MYOCD	ENST00000343344.8	c.2260G>C	p.Ala754Pro	missense_variant	13/13	1		ENSP00000341835.4
MYOCD	ENST00000443061.1	c.1390G>C	p.Ala464Pro	missense_variant	6/6	1		ENSP00000400148.2
ARHGAP44-AS1	ENST00000584772.1	n.732C>G		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2024

The c.2404G>C (p.A802P) alteration is located in exon 14 (coding exon 14) of the MYOCD gene. This alteration results from a G to C substitution at nucleotide position 2404, causing the alanine (A) at amino acid position 802 to be replaced by a proline (P). 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	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	.;D;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.4	.;M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.13	T;T;D
Polyphen		1.0	D;D;.
Vest4		0.50
MutPred		0.28		.;Gain of catalytic residue at A754 (P = 0.0254);.;
MVP		0.61
MPC		0.47
ClinPred		0.98	D
GERP RS		3.5
Varity_R		0.34
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr17-12666404;