chr11-77142700-C-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000260.4(MYO7A):c.19-9C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MYO7A
NM_000260.4 splice_polypyrimidine_tract, intron
NM_000260.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.9997
2
Clinical Significance
Conservation
PhyloP100: -1.10
Genes affected
MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.19-9C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000409709.9 | NP_000251.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.19-9C>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000260.4 | ENSP00000386331 | ||||
MYO7A | ENST00000409619.6 | c.-15-9C>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | ENSP00000386635 | |||||
MYO7A | ENST00000458637.6 | c.19-9C>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | ENSP00000392185 | P1 | ||||
MYO7A | ENST00000660626.1 | c.109-9C>A | splice_polypyrimidine_tract_variant, intron_variant | ENSP00000499401 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1448584Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 719510
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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0
AN:
1448584
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Cov.:
30
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0
AN XY:
719510
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 09, 2022 | This sequence change falls in intron 2 of the MYO7A gene. It does not directly change the encoded amino acid sequence of the MYO7A protein. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 998593). This variant has been observed in individual(s) with clinical features of M7O7A-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
DS_AL_spliceai
Position offset: 9
Find out detailed SpliceAI scores and Pangolin per-transcript scores at