chr17-75623807-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_001395058.1(MYO15B):c.8109T>G(p.Asp2703Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. 6/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00019 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MYO15B
NM_001395058.1 missense
NM_001395058.1 missense
Scores
2
3
6
Clinical Significance
Conservation
PhyloP100: 0.142
Genes affected
MYO15B (HGNC:14083): (myosin XVB) Predicted to enable ATP binding activity; actin binding activity; and cytoskeletal motor activity. Predicted to be located in brush border; cytoplasm; and cytoskeleton. Predicted to be part of myosin complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.797
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15B | NM_001395058.1 | c.8109T>G | p.Asp2703Glu | missense_variant | 54/64 | ENST00000645453.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15B | ENST00000645453.3 | c.8109T>G | p.Asp2703Glu | missense_variant | 54/64 | NM_001395058.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 151982Hom.: 0 Cov.: 33 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000195 AC: 107AN: 549598Hom.: 0 Cov.: 0 AF XY: 0.000188 AC XY: 56AN XY: 297578
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1AN: 151982Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74238
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | Dec 20, 2023 | The heterozygous p.Asp2703Glu variant in MYO15B was identified by our study in 1 individual with dysphagia, ptosis, increased muscle fatigability, and muscle weakness. This variant was detected in cis with another variant of uncertain significance (p.c.2651+2T>A) in MYO15B. While this gene is still lacking sufficient evidence to establish a gene-disease relationship, we believe this is a possible novel gene candidate for this phenotype. Given the limited information about this gene-disease relationship, the significance of the p.Asp2703Glu variant is uncertain. If you have any additional information about functional evidence or other individuals with this phenotype that also have variants in MYO15B we encourage you to reach out to us. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
N
Sift4G
Pathogenic
D;.
Vest4
GERP RS
Splicing
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.