chr14-23389065-G-T
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_002471.4(MYH6):c.3979-10C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000388 in 123,664 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: 𝑓 0.00039 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00032 ( 4 hom. )
Failed GnomAD Quality Control
Consequence
MYH6
NM_002471.4 splice_polypyrimidine_tract, intron
NM_002471.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.01427
2
Clinical Significance
Conservation
PhyloP100: 1.25
Genes affected
MYH6 (HGNC:7576): (myosin heavy chain 6) Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located approximately 4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3. [provided by RefSeq, Feb 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 14-23389065-G-T is Benign according to our data. Variant chr14-23389065-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 312856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23389065-G-T is described in Lovd as [Likely_benign].
BS2
High AC in GnomAd4 at 48 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.3979-10C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000405093.9 | NP_002462.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH6 | ENST00000405093.9 | c.3979-10C>A | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_002471.4 | ENSP00000386041 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000388 AC: 48AN: 123556Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.000409 AC: 78AN: 190566Hom.: 0 AF XY: 0.000499 AC XY: 52AN XY: 104112
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000317 AC: 447AN: 1408692Hom.: 4 Cov.: 36 AF XY: 0.000343 AC XY: 240AN XY: 699514
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GnomAD4 genome AF: 0.000388 AC: 48AN: 123664Hom.: 0 Cov.: 30 AF XY: 0.000395 AC XY: 24AN XY: 60728
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 06, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 22, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Hypertrophic cardiomyopathy 14 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 17, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jun 02, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at