rs201689300
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_017433.5(MYO3A):c.4439-12C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,582,256 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 (★★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
MYO3A
NM_017433.5 splice_polypyrimidine_tract, intron
NM_017433.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00001499
2
Clinical Significance
Conservation
PhyloP100: 0.201
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 -14 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 10-26193193-C-T is Benign according to our data. Variant chr10-26193193-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 178471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00115 (175/152182) while in subpopulation AFR AF= 0.00407 (169/41532). AF 95% confidence interval is 0.00357. There are 0 homozygotes in gnomad4. There are 68 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO3A | NM_017433.5 | c.4439-12C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000642920.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO3A | ENST00000642920.2 | c.4439-12C>T | splice_polypyrimidine_tract_variant, intron_variant | NM_017433.5 | P1 | ||||
MYO3A | ENST00000543632.5 | c.1777-18650C>T | intron_variant | 1 | |||||
MYO3A | ENST00000647478.1 | c.*1394-12C>T | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00116 AC: 176AN: 152064Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000351 AC: 88AN: 250478Hom.: 0 AF XY: 0.000251 AC XY: 34AN XY: 135404
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GnomAD4 exome AF: 0.000108 AC: 155AN: 1430074Hom.: 0 Cov.: 28 AF XY: 0.0000939 AC XY: 67AN XY: 713606
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GnomAD4 genome ? AF: 0.00115 AC: 175AN: 152182Hom.: 0 Cov.: 31 AF XY: 0.000914 AC XY: 68AN XY: 74400
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 28, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 11, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 24, 2016 | 4439-12C>T in intron 31 of MYO3A: This variant is not expected to have clinical significance because it has been identified in 0.6% (51/9046) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201689300). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at