17-10628691-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6BS2_Supporting
The NM_002470.4(MYH3):c.5797-12C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,614,188 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002470.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH3 | NM_002470.4 | c.5797-12C>G | intron_variant | Intron 40 of 40 | ENST00000583535.6 | NP_002461.2 | ||
MYH3 | XM_011523870.4 | c.5797-12C>G | intron_variant | Intron 40 of 40 | XP_011522172.1 | |||
MYH3 | XM_011523871.3 | c.5797-12C>G | intron_variant | Intron 40 of 40 | XP_011522173.1 | |||
MYH3 | XM_047436127.1 | c.5797-12C>G | intron_variant | Intron 42 of 42 | XP_047292083.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH3 | ENST00000583535.6 | c.5797-12C>G | intron_variant | Intron 40 of 40 | 5 | NM_002470.4 | ENSP00000464317.1 | |||
MYH3 | ENST00000577963.1 | n.339-12C>G | intron_variant | Intron 1 of 1 | 2 | |||||
MYH3 | ENST00000579928.2 | n.327-12C>G | intron_variant | Intron 2 of 2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000598 AC: 91AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000177 AC: 44AN: 249140Hom.: 0 AF XY: 0.0000964 AC XY: 13AN XY: 134866
GnomAD4 exome AF: 0.0000657 AC: 96AN: 1461868Hom.: 0 Cov.: 30 AF XY: 0.0000578 AC XY: 42AN XY: 727240
GnomAD4 genome AF: 0.000597 AC: 91AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44AN XY: 74496
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
- -
Has not been previously published as pathogenic or benign to our knowledge; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. -
Freeman-Sheldon syndrome Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Distal arthrogryposis type 2B1 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at