rs34918608
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_017433.5(MYO3A):c.3094G>A(p.Ala1032Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00895 in 1,613,232 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0080 ( 11 hom., cov: 33)
Exomes 𝑓: 0.0090 ( 83 hom. )
Consequence
MYO3A
NM_017433.5 missense
NM_017433.5 missense
Scores
6
7
Clinical Significance
Conservation
PhyloP100: 5.53
Genes affected
MYO3A (HGNC:7601): (myosin IIIA) The protein encoded by this gene belongs to the myosin superfamily. Myosins are actin-dependent motor proteins and are categorized into conventional myosins (class II) and unconventional myosins (classes I and III through XV) based on their variable C-terminal cargo-binding domains. Class III myosins, such as this one, have a kinase domain N-terminal to the conserved N-terminal motor domains and are expressed in photoreceptors. The protein encoded by this gene plays an important role in hearing in humans. Three different recessive, loss of function mutations in the encoded protein have been shown to cause nonsyndromic progressive hearing loss. Expression of this gene is highly restricted, with the strongest expression in retina and cochlea. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.011166692).
BP6
?
Variant 10-26166161-G-A is Benign according to our data. Variant chr10-26166161-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 45806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-26166161-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00802 (1221/152244) while in subpopulation NFE AF= 0.011 (745/68010). AF 95% confidence interval is 0.0103. There are 11 homozygotes in gnomad4. There are 638 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 11 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO3A | NM_017433.5 | c.3094G>A | p.Ala1032Thr | missense_variant | 27/35 | ENST00000642920.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO3A | ENST00000642920.2 | c.3094G>A | p.Ala1032Thr | missense_variant | 27/35 | NM_017433.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00803 AC: 1221AN: 152126Hom.: 11 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00815 AC: 2047AN: 251272Hom.: 15 AF XY: 0.00802 AC XY: 1089AN XY: 135814
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GnomAD4 exome AF: 0.00904 AC: 13214AN: 1460988Hom.: 83 Cov.: 30 AF XY: 0.00901 AC XY: 6550AN XY: 726900
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GnomAD4 genome ? AF: 0.00802 AC: 1221AN: 152244Hom.: 11 Cov.: 33 AF XY: 0.00857 AC XY: 638AN XY: 74430
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36
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34
ESP6500AA
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73
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1029
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
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 | Ala1032Thr in Exon 27 of MYO3A: This variant is not expected to have clinical si gnificance because it has been identified in 0.8% (56/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs34918608). - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 14, 2015 | - - |
Autosomal recessive nonsyndromic hearing loss 30 Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 06, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 30, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | MYO3A: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 24, 2018 | This variant is associated with the following publications: (PMID: 17344846) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Benign
T
Polyphen
P;P
Vest4
0.38
MVP
0.86
MPC
0.064
ClinPred
T
GERP RS
Varity_R
gMVP
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