rs35555631
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001164508.2(NEB):c.8072G>C(p.Arg2691Pro) variant causes a missense change involving the alteration of a 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: 33)
Consequence
NEB
NM_001164508.2 missense
NM_001164508.2 missense
Scores
8
8
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.75
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 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.855
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NEB | ENST00000397345.8 | c.8072G>C | p.Arg2691Pro | missense_variant | Exon 58 of 182 | 5 | NM_001164508.2 | ENSP00000380505.3 | ||
| NEB | ENST00000427231.7 | c.8072G>C | p.Arg2691Pro | missense_variant | Exon 58 of 182 | 5 | NM_001164507.2 | ENSP00000416578.2 | ||
| NEB | ENST00000409198.5 | c.8072G>C | p.Arg2691Pro | missense_variant | Exon 58 of 150 | 5 | ENSP00000386259.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.;D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;.;.
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;.;M;M;M;M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.;D;D;.;.
REVEL
Uncertain
Sift
Uncertain
D;D;.;D;D;.;.
Sift4G
Pathogenic
D;D;D;D;D;D;D
Polyphen
1.0
.;.;.;.;D;.;.
Vest4
MutPred
Loss of catalytic residue at R2691 (P = 0.012);Loss of catalytic residue at R2691 (P = 0.012);Loss of catalytic residue at R2691 (P = 0.012);Loss of catalytic residue at R2691 (P = 0.012);Loss of catalytic residue at R2691 (P = 0.012);Loss of catalytic residue at R2691 (P = 0.012);Loss of catalytic residue at R2691 (P = 0.012);
MVP
MPC
0.40
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
Publications
No publications associated with this variant yet.