rs201636991
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001164507.2(NEB):c.5364G>T(p.Trp1788Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NEB
NM_001164507.2 missense
NM_001164507.2 missense
Scores
6
8
4
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.48
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.796
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.5364G>T | p.Trp1788Cys | missense_variant | 44/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.5364G>T | p.Trp1788Cys | missense_variant | 44/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.5364G>T | p.Trp1788Cys | missense_variant | 44/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.5364G>T | p.Trp1788Cys | missense_variant | 44/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.5364G>T | p.Trp1788Cys | missense_variant | 44/150 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1454248Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 722492
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1454248
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
722492
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;.;.
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;.;M;M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;D;D;.;.
REVEL
Uncertain
Sift
Uncertain
D;D;.;D;D;.;.
Sift4G
Uncertain
D;D;D;D;D;D;D
Polyphen
1.0
.;.;.;.;D;.;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0693);Loss of MoRF binding (P = 0.0693);Loss of MoRF binding (P = 0.0693);Loss of MoRF binding (P = 0.0693);Loss of MoRF binding (P = 0.0693);Loss of MoRF binding (P = 0.0693);Loss of MoRF binding (P = 0.0693);
MVP
MPC
0.36
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at