chr11-77181444-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000260.4(MYO7A):c.2759G>T(p.Arg920Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,605,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.2759G>T | p.Arg920Leu | missense_variant | Exon 23 of 49 | 1 | NM_000260.4 | ENSP00000386331.3 | ||
MYO7A | ENST00000458637.6 | c.2759G>T | p.Arg920Leu | missense_variant | Exon 23 of 49 | 1 | ENSP00000392185.2 | |||
MYO7A | ENST00000409619.6 | c.2726G>T | p.Arg909Leu | missense_variant | Exon 24 of 50 | 1 | ENSP00000386635.2 | |||
MYO7A | ENST00000458169.2 | c.302G>T | p.Arg101Leu | missense_variant | Exon 3 of 29 | 1 | ENSP00000417017.2 | |||
MYO7A | ENST00000670577.1 | n.599G>T | non_coding_transcript_exon_variant | Exon 6 of 32 | ENSP00000499323.1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152244Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000776 AC: 18AN: 231936Hom.: 0 AF XY: 0.0000791 AC XY: 10AN XY: 126444
GnomAD4 exome AF: 0.000131 AC: 191AN: 1452804Hom.: 0 Cov.: 33 AF XY: 0.000109 AC XY: 79AN XY: 721898
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74384
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
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not specified Uncertain:1
The p.Arg920Leu variant in MYO7A has not been previously reported in individuals with hearing loss. This variant has been identified in 9/29234 European chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs565162134). Computational prediction tools and conservation analyses sug gest that this variant may not impact the protein, though this information is no t predictive enough to rule out pathogenicity. In summary, the clinical signific ance of the p.Arg920Leu variant is uncertain. -
Usher syndrome type 1B Uncertain:1
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MYO7A-related disorder Uncertain:1
The MYO7A c.2759G>T variant is predicted to result in the amino acid substitution p.Arg920Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at