rs17546153
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_005379.4(MYO1A):āc.1185T>Cā(p.Phe395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,613,914 control chromosomes in the GnomAD database, including 1,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.030 ( 89 hom., cov: 32)
Exomes š: 0.037 ( 1226 hom. )
Consequence
MYO1A
NM_005379.4 synonymous
NM_005379.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.49
Genes affected
MYO1A (HGNC:7595): (myosin IA) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional skeletal muscle myosin-1 (MYH1). Unconventional myosins contain the basic domains characteristic of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with autosomal dominant deafness. Alternatively spliced variants have been found for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 12-57041268-A-G is Benign according to our data. Variant chr12-57041268-A-G is described in ClinVar as [Benign]. Clinvar id is 45306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-57041268-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.49 with no splicing effect.
BA1
?
GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO1A | NM_005379.4 | c.1185T>C | p.Phe395= | synonymous_variant | 14/28 | ENST00000300119.8 | |
MYO1A | NM_001256041.2 | c.1185T>C | p.Phe395= | synonymous_variant | 15/29 | ||
MYO1A | XM_047428876.1 | c.1185T>C | p.Phe395= | synonymous_variant | 15/29 | ||
MYO1A | XM_011538373.3 | c.1185T>C | p.Phe395= | synonymous_variant | 14/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO1A | ENST00000300119.8 | c.1185T>C | p.Phe395= | synonymous_variant | 14/28 | 1 | NM_005379.4 | P1 | |
MYO1A | ENST00000442789.6 | c.1185T>C | p.Phe395= | synonymous_variant | 15/29 | 1 | P1 | ||
MYO1A | ENST00000554234.5 | c.699T>C | p.Phe233= | synonymous_variant, NMD_transcript_variant | 10/24 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0297 AC: 4517AN: 152164Hom.: 89 Cov.: 32
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GnomAD3 exomes AF: 0.0356 AC: 8947AN: 251328Hom.: 224 AF XY: 0.0374 AC XY: 5084AN XY: 135812
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GnomAD4 exome AF: 0.0372 AC: 54366AN: 1461632Hom.: 1226 Cov.: 31 AF XY: 0.0373 AC XY: 27142AN XY: 727120
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GnomAD4 genome ? AF: 0.0296 AC: 4513AN: 152282Hom.: 89 Cov.: 32 AF XY: 0.0291 AC XY: 2167AN XY: 74458
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Phe395Phe in Exon 14 of MYO1A: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 4.6% (325/7020) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs17546153). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 03, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at