rs372223659
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_000260.4(MYO7A):c.2928G>A(p.Glu976=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,284 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
MYO7A
NM_000260.4 synonymous
NM_000260.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.71
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 Benign. Variant got -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 11-77181974-G-A is Benign according to our data. Variant chr11-77181974-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 504645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77181974-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=1.71 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.2928G>A | p.Glu976= | synonymous_variant | 24/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.2928G>A | p.Glu976= | synonymous_variant | 24/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 151936Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000445 AC: 11AN: 247318Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134580
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461230Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 726880
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152054Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9AN XY: 74324
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Glu976Glu in Exon 24 of MYO7A: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.1% (3/3580) of Afri can American chromosomes from a broad population by the NHLBI Exome Sequencing P roject (http://evs.gs.washington.edu/EVS). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at