rs1553683577
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP3
The NM_001164508.2(NEB):c.21213_21218delGTATAA(p.Tyr7072_Lys7073del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NEB
NM_001164508.2 disruptive_inframe_deletion
NM_001164508.2 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.01
Genes affected
NEB (HGNC:7720): (nebulin) This gene encodes nebulin, a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein. The encoded protein contains approximately 30-amino acid long modules that can be classified into 7 types and other repeated modules. Protein isoform sizes vary from 600 to 800 kD due to alternative splicing that is tissue-, species-,and developmental stage-specific. Of the 183 exons in the nebulin gene, at least 43 are alternatively spliced, although exons 143 and 144 are not found in the same transcript. Of the several thousand transcript variants predicted for nebulin, the RefSeq Project has decided to create three representative RefSeq records. Mutations in this gene are associated with recessive nemaline myopathy. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001164508.2.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.21213_21218delGTATAA | p.Tyr7072_Lys7073del | disruptive_inframe_deletion | Exon 142 of 182 | ENST00000427231.7 | NP_001157979.2 | |
NEB | NM_001164508.2 | c.21213_21218delGTATAA | p.Tyr7072_Lys7073del | disruptive_inframe_deletion | Exon 142 of 182 | ENST00000397345.8 | NP_001157980.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.21213_21218delGTATAA | p.Tyr7072_Lys7073del | disruptive_inframe_deletion | Exon 142 of 182 | 5 | NM_001164508.2 | ENSP00000380505.3 | ||
NEB | ENST00000427231.7 | c.21213_21218delGTATAA | p.Tyr7072_Lys7073del | disruptive_inframe_deletion | Exon 142 of 182 | 5 | NM_001164507.2 | ENSP00000416578.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1431310Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 710340
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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0
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1431310
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0
AN XY:
710340
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nemaline myopathy 2 Uncertain:1
Aug 31, 2021
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
Calibrated prediction
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at