17-18136486-G-A
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_016239.4(MYO15A):c.4655+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,613,626 control chromosomes in the GnomAD database, including 11 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 0.0016 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 10 hom. )
Consequence
MYO15A
NM_016239.4 intron
NM_016239.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.586
Genes affected
MYO15A (HGNC:7594): (myosin XVA) This gene encodes an unconventional myosin. This protein differs from other myosins in that it has a long N-terminal extension preceding the conserved motor domain. Studies in mice suggest that this protein is necessary for actin organization in the hair cells of the cochlea. Mutations in this gene have been associated with profound, congenital, neurosensory, nonsyndromal deafness. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Read-through transcripts containing an upstream gene and this gene have been identified, but they are not thought to encode a fusion protein. Several alternatively spliced transcript variants have been described, but their full length sequences have not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 17-18136486-G-A is Benign according to our data. Variant chr17-18136486-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 164521.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2, Likely_benign=1}. Variant chr17-18136486-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00157 (239/152274) while in subpopulation EAS AF= 0.0247 (128/5180). AF 95% confidence interval is 0.0212. There are 1 homozygotes in gnomad4. There are 140 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.4655+11G>A | intron_variant | ENST00000647165.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.4655+11G>A | intron_variant | NM_016239.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00157 AC: 239AN: 152156Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00285 AC: 709AN: 248990Hom.: 2 AF XY: 0.00277 AC XY: 374AN XY: 135148
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GnomAD4 exome AF: 0.00111 AC: 1623AN: 1461352Hom.: 10 Cov.: 32 AF XY: 0.00110 AC XY: 802AN XY: 727010
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GnomAD4 genome AF: 0.00157 AC: 239AN: 152274Hom.: 1 Cov.: 33 AF XY: 0.00188 AC XY: 140AN XY: 74448
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 07, 2019 | - - |
Autosomal recessive nonsyndromic hearing loss 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 17, 2015 | 4655+11G>A in Intron 14 of MYO15A: This variant is not expected to have clinical significance because has been identified in 2.6% (223/8612) of East Asian chrom osomes including 1 homozygote by the by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs117021471). - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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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