NM_002471.4:c.3979-8dupC
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_002471.4(MYH6):c.3979-8dupC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002471.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.3979-8dupC | splice_region_variant, intron_variant | Intron 28 of 38 | ENST00000405093.9 | NP_002462.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00714 AC: 825AN: 115566Hom.: 5 Cov.: 0
GnomAD3 exomes AF: 0.00589 AC: 822AN: 139674Hom.: 0 AF XY: 0.00638 AC XY: 487AN XY: 76278
GnomAD4 exome AF: 0.00367 AC: 3873AN: 1056040Hom.: 0 Cov.: 0 AF XY: 0.00410 AC XY: 2159AN XY: 526192
GnomAD4 genome AF: 0.00713 AC: 825AN: 115680Hom.: 5 Cov.: 0 AF XY: 0.00753 AC XY: 428AN XY: 56842
ClinVar
Submissions by phenotype
not specified Benign:4Other:1
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Variant summary: MYH6 c.3979-8dupC alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0059 in 139674 control chromosomes. The observed variant frequency is approximately 235 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYH6 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.3979-8dupC in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign. -
Dilated Cardiomyopathy, Dominant Uncertain:1
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Atrial septal defect Uncertain:1
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Hypertrophic cardiomyopathy Uncertain:1
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Hypertrophic cardiomyopathy 14 Benign:1
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Cardiomyopathy Benign:1
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not provided Benign:1
MYH6: BP4, BS1 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at