chr14-23417310-G-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_000257.4(MYH7):c.4362C>T(p.Ala1454Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,596 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 (★). Synonymous variant affecting the same amino acid position (i.e. A1454A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
MYH7
NM_000257.4 synonymous
NM_000257.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.80
Publications
1 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: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 14-23417310-G-A is Benign according to our data. Variant chr14-23417310-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1137138.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.8 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000257.4. 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.4362C>T | p.Ala1454Ala | synonymous | Exon 32 of 40 | NP_000248.2 | ||
| MYH7 | NM_001407004.1 | c.4362C>T | p.Ala1454Ala | synonymous | Exon 31 of 39 | NP_001393933.1 | |||
| MHRT | NR_126491.1 | n.750G>A | non_coding_transcript_exon | Exon 5 of 6 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MYH7 | ENST00000355349.4 | TSL:1 MANE Select | c.4362C>T | p.Ala1454Ala | synonymous | Exon 32 of 40 | ENSP00000347507.3 | ||
| MYH7 | ENST00000713768.1 | c.4362C>T | p.Ala1454Ala | synonymous | Exon 32 of 41 | ENSP00000519070.1 | |||
| MYH7 | ENST00000713769.1 | c.4362C>T | p.Ala1454Ala | synonymous | Exon 31 of 39 | ENSP00000519071.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000399 AC: 1AN: 250900 AF XY: 0.00000737 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
250900
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461596Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727084 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1461596
Hom.:
Cov.:
34
AF XY:
AC XY:
1
AN XY:
727084
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
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:
86250
European-Finnish (FIN)
AF:
AC:
0
AN:
53318
Middle Eastern (MID)
AF:
AC:
0
AN:
5602
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1112012
Other (OTH)
AF:
AC:
0
AN:
60376
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
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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