17-12763317-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001146312.3(MYOCD):​c.2634C>T​(p.Ser878Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,608,058 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 94 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 76 hom. )

Consequence

MYOCD
NM_001146312.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.76
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 17-12763317-C-T is Benign according to our data. Variant chr17-12763317-C-T is described in ClinVar as [Benign]. Clinvar id is 780416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.76 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0557 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYOCDNM_001146312.3 linkuse as main transcriptc.2634C>T p.Ser878Ser synonymous_variant 14/14 ENST00000425538.6 NP_001139784.1 Q8IZQ8-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYOCDENST00000425538.6 linkuse as main transcriptc.2634C>T p.Ser878Ser synonymous_variant 14/141 NM_001146312.3 ENSP00000401678.1 Q8IZQ8-3
MYOCDENST00000343344.8 linkuse as main transcriptc.2490C>T p.Ser830Ser synonymous_variant 13/131 ENSP00000341835.4 Q8IZQ8-1
MYOCDENST00000443061.1 linkuse as main transcriptc.1620C>T p.Ser540Ser synonymous_variant 6/61 ENSP00000400148.2 Q6N065
ARHGAP44-AS1ENST00000584772.1 linkuse as main transcriptn.502G>A non_coding_transcript_exon_variant 2/21

Frequencies

GnomAD3 genomes
AF:
0.0170
AC:
2578
AN:
152030
Hom.:
92
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0574
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00649
Gnomad ASJ
AF:
0.0104
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000529
Gnomad OTH
AF:
0.0144
GnomAD3 exomes
AF:
0.00499
AC:
1225
AN:
245680
Hom.:
39
AF XY:
0.00368
AC XY:
488
AN XY:
132752
show subpopulations
Gnomad AFR exome
AF:
0.0595
Gnomad AMR exome
AF:
0.00279
Gnomad ASJ exome
AF:
0.00936
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000237
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000574
Gnomad OTH exome
AF:
0.00152
GnomAD4 exome
AF:
0.00212
AC:
3092
AN:
1455910
Hom.:
76
Cov.:
31
AF XY:
0.00188
AC XY:
1358
AN XY:
724022
show subpopulations
Gnomad4 AFR exome
AF:
0.0627
Gnomad4 AMR exome
AF:
0.00309
Gnomad4 ASJ exome
AF:
0.00830
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000211
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000273
Gnomad4 OTH exome
AF:
0.00533
GnomAD4 genome
AF:
0.0170
AC:
2590
AN:
152148
Hom.:
94
Cov.:
32
AF XY:
0.0169
AC XY:
1257
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.0576
Gnomad4 AMR
AF:
0.00642
Gnomad4 ASJ
AF:
0.0104
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000529
Gnomad4 OTH
AF:
0.0142
Alfa
AF:
0.00699
Hom.:
16
Bravo
AF:
0.0195
Asia WGS
AF:
0.00520
AC:
18
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 09, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.24
DANN
Benign
0.58

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.

Other links and lift over

dbSNP: rs28730829; hg19: chr17-12666634; COSMIC: COSV58497071; API