14-23417598-G-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The ENST00000355349.4(MYH7):c.4258C>A(p.Arg1420Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
MYH7
ENST00000355349.4 synonymous
ENST00000355349.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.77
Publications
14 publications found
Genes affected
MYH7 (HGNC:7577): (myosin heavy chain 7) Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]
MHRT (HGNC:51291): (myosin heavy chain associated RNA transcript) This gene encodes a spliced long non-coding RNA that may act as a cardioprotective agent in the heart. Based on a study of a similar gene in mouse, the encoded transcript may regulate chromatin remodeling by acting as a decoy to the BRG1 chromatin repressor complex thus preventing it from binding to its genomic targets. Blocking the actions of BRG1 could be crucial in protecting the heart from pathological hypertrophy. [provided by RefSeq, Dec 2014]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
Variant 14-23417598-G-T is Benign according to our data. Variant chr14-23417598-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1978459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.77 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000355349.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MYH7 | NM_000257.4 | MANE Select | c.4258C>A | p.Arg1420Arg | synonymous | Exon 31 of 40 | NP_000248.2 | ||
| MYH7 | NM_001407004.1 | c.4258C>A | p.Arg1420Arg | synonymous | Exon 30 of 39 | NP_001393933.1 | |||
| MHRT | NR_126491.1 | n.*3G>T | downstream_gene | N/A |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MYH7 | ENST00000355349.4 | TSL:1 MANE Select | c.4258C>A | p.Arg1420Arg | synonymous | Exon 31 of 40 | ENSP00000347507.3 | ||
| MYH7 | ENST00000713768.1 | c.4258C>A | p.Arg1420Arg | synonymous | Exon 31 of 41 | ENSP00000519070.1 | |||
| MYH7 | ENST00000713769.1 | c.4258C>A | p.Arg1420Arg | synonymous | Exon 30 of 39 | ENSP00000519071.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460406Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3AN XY: 726524 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1460406
Hom.:
Cov.:
34
AF XY:
AC XY:
3
AN XY:
726524
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33434
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86186
European-Finnish (FIN)
AF:
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
AC:
0
AN:
4528
European-Non Finnish (NFE)
AF:
AC:
5
AN:
1112006
Other (OTH)
AF:
AC:
0
AN:
60276
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
-
1
Cardiomyopathy (1)
-
-
1
Hypertrophic cardiomyopathy (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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