rs727505229
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_017433.5(MYO3A):āc.1038A>Gā(p.Leu346=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,058 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 Likely benign (ā ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
MYO3A
NM_017433.5 synonymous
NM_017433.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.249
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 10-26067059-A-G is Benign according to our data. Variant chr10-26067059-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 179933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-26067059-A-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.249 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO3A | NM_017433.5 | c.1038A>G | p.Leu346= | synonymous_variant | 11/35 | ENST00000642920.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO3A | ENST00000642920.2 | c.1038A>G | p.Leu346= | synonymous_variant | 11/35 | NM_017433.5 | P1 | ||
MYO3A | ENST00000543632.5 | c.1038A>G | p.Leu346= | synonymous_variant | 10/17 | 1 | |||
MYO3A | ENST00000642197.1 | n.1242A>G | non_coding_transcript_exon_variant | 11/27 | |||||
MYO3A | ENST00000647478.1 | c.1038A>G | p.Leu346= | synonymous_variant, NMD_transcript_variant | 10/30 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251262Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135820
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GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1456058Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 724662
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 07, 2014 | Leu346Leu in exon 11 of MYO3A: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 05, 2021 | - - |
Computational scores
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Name
Calibrated prediction
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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