17-18157211-A-C
Variant names:
Variant summary
Our verdict is . The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
Likely benign
The NM_016239.4(MYO15A):c.8769A>C(p.Arg2923Arg) 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 1,456,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene MYO15A is included in the ClinGen Criteria Specification Registry.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
MYO15A
NM_016239.4 synonymous
NM_016239.4 synonymous
Scores
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.49
Publications
0 publications found
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]
MYO15A Gene-Disease associations (from GenCC):
- autosomal recessive nonsyndromic hearing loss 3Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
- nonsyndromic genetic hearing lossInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
new If you want to explore the variant's impact on the transcript NM_016239.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
ACMG classification
Specifications for MYO15A are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP7
Synonymous conserved (PhyloP=1.49 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_016239.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MYO15A | MANE Select | c.8769A>C | p.Arg2923Arg | synonymous | Exon 50 of 66 | ENSP00000495481.1 | Q9UKN7-1 | ||
| MYO15A | TSL:2 | c.561A>C | p.Arg187Arg | synonymous | Exon 8 of 24 | ENSP00000408800.3 | Q9UKN7-2 | ||
| MYO15A | c.561A>C | p.Arg187Arg | synonymous | Exon 8 of 23 | ENSP00000495720.1 | A0A2R8Y712 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1456024Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 723744 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1456024
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
723744
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33302
American (AMR)
AF:
AC:
0
AN:
44122
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25998
East Asian (EAS)
AF:
AC:
0
AN:
39358
South Asian (SAS)
AF:
AC:
0
AN:
85232
European-Finnish (FIN)
AF:
AC:
0
AN:
52814
Middle Eastern (MID)
AF:
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1109360
Other (OTH)
AF:
AC:
0
AN:
60082
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
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70-75
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
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