14-23390171-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_002471.4(MYH6):c.3618C>T(p.Gly1206=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,607,756 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G1206G) has been classified as Benign.
Frequency
Consequence
NM_002471.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.3618C>T | p.Gly1206= | synonymous_variant | 26/39 | ENST00000405093.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH6 | ENST00000405093.9 | c.3618C>T | p.Gly1206= | synonymous_variant | 26/39 | 5 | NM_002471.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000396 AC: 6AN: 151544Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249096Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134848
GnomAD4 exome AF: 0.0000350 AC: 51AN: 1456212Hom.: 0 Cov.: 34 AF XY: 0.0000401 AC XY: 29AN XY: 723894
GnomAD4 genome AF: 0.0000396 AC: 6AN: 151544Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 73964
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | This sequence change affects codon 1206 of the MYH6 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MYH6 protein. This variant is present in population databases (rs765103086, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 565499). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Dilated cardiomyopathy 1EE;C2750467:Hypertrophic cardiomyopathy 14;C3279790:Atrial septal defect 3;C3279791:Sick sinus syndrome 3, susceptibility to;C3495498:Hypertrophic cardiomyopathy 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 12, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2022 | The c.3618C>T variant (also known as p.G1206G), located in coding exon 24 of the MYH6 gene, results from a C to T substitution at nucleotide position 3618. This nucleotide substitution does not change the glycine at codon 1206. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at