17-10628614-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6BS2_Supporting
The NM_002470.4(MYH3):c.*39G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000789 in 1,608,862 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 3_prime_UTR
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH3 | NM_002470.4 | c.*39G>A | 3_prime_UTR_variant | Exon 41 of 41 | ENST00000583535.6 | NP_002461.2 | ||
MYH3 | XM_011523870.4 | c.*39G>A | 3_prime_UTR_variant | Exon 41 of 41 | XP_011522172.1 | |||
MYH3 | XM_011523871.3 | c.*39G>A | 3_prime_UTR_variant | Exon 41 of 41 | XP_011522173.1 | |||
MYH3 | XM_047436127.1 | c.*39G>A | 3_prime_UTR_variant | Exon 43 of 43 | XP_047292083.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH3 | ENST00000583535 | c.*39G>A | 3_prime_UTR_variant | Exon 41 of 41 | 5 | NM_002470.4 | ENSP00000464317.1 | |||
MYH3 | ENST00000577963.1 | n.404G>A | non_coding_transcript_exon_variant | Exon 2 of 2 | 2 | |||||
MYH3 | ENST00000579928.2 | n.392G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000116 AC: 29AN: 249450Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135020
GnomAD4 exome AF: 0.0000796 AC: 116AN: 1456598Hom.: 0 Cov.: 29 AF XY: 0.0000896 AC XY: 65AN XY: 725132
GnomAD4 genome AF: 0.0000722 AC: 11AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74460
ClinVar
Submissions by phenotype
Distal arthrogryposis type 2B1 Uncertain: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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
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 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