chr11-77204065-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000260.4(MYO7A):c.5327-11A>G variant causes a intron change involving the alteration of a 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 Conflicting classifications of pathogenicity (no stars). There are indicators that this mutation may affect the branch point..
Frequency
Consequence
NM_000260.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.5327-11A>G | intron_variant | Intron 38 of 48 | 1 | NM_000260.4 | ENSP00000386331.3 | |||
MYO7A | ENST00000458637.6 | c.5213-11A>G | intron_variant | Intron 38 of 48 | 1 | ENSP00000392185.2 | ||||
MYO7A | ENST00000409619.6 | c.5180-11A>G | intron_variant | Intron 39 of 49 | 1 | ENSP00000386635.2 | ||||
MYO7A | ENST00000458169.2 | c.2753-11A>G | intron_variant | Intron 18 of 28 | 1 | ENSP00000417017.2 | ||||
MYO7A | ENST00000670577.1 | n.3167-25A>G | intron_variant | Intron 21 of 31 | ENSP00000499323.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1441200Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 714368
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Rare genetic deafness Pathogenic:1
The p.5327-11A>G variant in MYO7A has been identified by our laboratory in one i ndividual with a clinical diagnosis of Usher syndrome type I, who carried a seco nd pathogenic variant in the same gene. It was absent from large population stud ies. This variant is located in the 3' splice region but does not affect the inv ariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes aff ect splicing. Although position -11 of the major splice consensus sequence is ty pically a T or C, this intron better matches a minor splice consensus sequence w hich very rarely has a G at -11. Therefore, this variant could impact splicing a nd lead to a disrupted transcript. In summary, although additional studies are r equired to fully establish its clinical significance, the p.5327-11A>G variant i s likely pathogenic. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at