rs727505114
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000260.4(MYO7A):c.5857-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,609,518 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 Uncertain significance (★★).
Frequency
Consequence
NM_000260.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.5857-3C>A | splice_region_variant, intron_variant | Intron 42 of 48 | 1 | NM_000260.4 | ENSP00000386331.3 | |||
MYO7A | ENST00000458637.6 | c.5743-3C>A | splice_region_variant, intron_variant | Intron 42 of 48 | 1 | ENSP00000392185.2 | ||||
MYO7A | ENST00000409619.6 | c.5710-3C>A | splice_region_variant, intron_variant | Intron 43 of 49 | 1 | ENSP00000386635.2 | ||||
MYO7A | ENST00000458169.2 | c.3283-3C>A | splice_region_variant, intron_variant | Intron 22 of 28 | 1 | ENSP00000417017.2 | ||||
MYO7A | ENST00000670577.1 | n.*455-3C>A | splice_region_variant, intron_variant | Intron 25 of 31 | ENSP00000499323.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152214Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 247122Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134124
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1457304Hom.: 0 Cov.: 32 AF XY: 0.00000965 AC XY: 7AN XY: 725056
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152214Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74360
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant classified as Uncertain Significance - Favor Pathogenic. The 5857-3C>A v ariant in MYO7A has been reported one individual with hearing loss but was absen t in large population studies (LMM unpublished data). A second variant in MYO7A was not identified in this individual. This variant is located in the 3' splice region. Computational tools suggest an impact to splicing. However, this informa tion is not predictive enough to determine pathogenicity. In summary, while the available data on the 5857-3C>A variant is suspicious for pathogenicity, the cli nical significance of this variant is uncertain. -
Usher syndrome type 1;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
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Usher syndrome type 1B Uncertain:1
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not provided Uncertain:1
This sequence change falls in intron 42 of the MYO7A gene. It does not directly change the encoded amino acid sequence of the MYO7A protein. It affects a nucleotide within the consensus splice site. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 179770). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at