rs561295735
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_005379.4(MYO1A):c.522C>T(p.Leu174=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,614,114 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00018 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 1 hom. )
Consequence
MYO1A
NM_005379.4 synonymous
NM_005379.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.72
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 12-57046882-G-A is Benign according to our data. Variant chr12-57046882-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 164599.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-1.72 with no splicing effect.
BS2
High AC in GnomAd4 at 27 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MYO1A | NM_005379.4 | c.522C>T | p.Leu174= | synonymous_variant | 7/28 | ENST00000300119.8 | NP_005370.1 | |
| MYO1A | NM_001256041.2 | c.522C>T | p.Leu174= | synonymous_variant | 8/29 | NP_001242970.1 | ||
| MYO1A | XM_047428876.1 | c.522C>T | p.Leu174= | synonymous_variant | 8/29 | XP_047284832.1 | ||
| MYO1A | XM_011538373.3 | c.522C>T | p.Leu174= | synonymous_variant | 7/25 | XP_011536675.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MYO1A | ENST00000300119.8 | c.522C>T | p.Leu174= | synonymous_variant | 7/28 | 1 | NM_005379.4 | ENSP00000300119 | P1 | |
| MYO1A | ENST00000442789.6 | c.522C>T | p.Leu174= | synonymous_variant | 8/29 | 1 | ENSP00000393392 | P1 | ||
| MYO1A | ENST00000492945.5 | c.-21+3005C>T | intron_variant | 4 | ENSP00000452229 | |||||
| MYO1A | ENST00000554234.5 | c.36C>T | p.Leu12= | synonymous_variant, NMD_transcript_variant | 3/24 | 5 | ENSP00000451033 |
Frequencies
GnomAD3 genomes 0.000177 AC: 27AN: 152138Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000310 AC: 78AN: 251394Hom.: 0 AF XY: 0.000390 AC XY: 53AN XY: 135860
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GnomAD4 exome AF: 0.000161 AC: 236AN: 1461858Hom.: 1 Cov.: 32 AF XY: 0.000224 AC XY: 163AN XY: 727230
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GnomAD4 genome 0.000177 AC: 27AN: 152256Hom.: 1 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74466
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Nonsyndromic Hearing Loss, Dominant Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 04, 2013 | The Leu174Leu variant in exon 07 of MYO1A: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice junction. - |
MYO1A-related disorder Benign:1
| Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 12, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at