14-23389062-AGGG-AGGGGG
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_002471.4(MYH6):c.3979-9_3979-8dupCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_002471.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.3979-9_3979-8dupCC | splice_region_variant, intron_variant | Intron 28 of 38 | ENST00000405093.9 | NP_002462.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000259 AC: 3AN: 115624Hom.: 0 Cov.: 0
GnomAD4 exome AF: 0.0000255 AC: 27AN: 1059776Hom.: 0 Cov.: 0 AF XY: 0.0000208 AC XY: 11AN XY: 528120
GnomAD4 genome AF: 0.0000259 AC: 3AN: 115624Hom.: 0 Cov.: 0 AF XY: 0.0000176 AC XY: 1AN XY: 56768
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: MYH6 c.3979-9_3979-8dupCC alters multiple nucleotides in a repeat Cs region located close to a canonical splice site. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 139674 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3979-9_3979-8dupCC in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. However, several del/dup variants have been found in this region and classified as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign. -
Hypertrophic cardiomyopathy 14 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at