rs753691207
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PP3_ModerateBP6_Moderate
The NM_001164508.2(NEB):āc.2987T>Cā(p.Ile996Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,461,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.000013 ( 0 hom. )
Consequence
NEB
NM_001164508.2 missense
NM_001164508.2 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 6.45
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.904
BP6
Variant 2-151680785-A-G is Benign according to our data. Variant chr2-151680785-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 565923.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.2987T>C | p.Ile996Thr | missense_variant | 30/182 | ENST00000427231.7 | NP_001157979.2 | |
NEB | NM_001164508.2 | c.2987T>C | p.Ile996Thr | missense_variant | 30/182 | ENST00000397345.8 | NP_001157980.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.2987T>C | p.Ile996Thr | missense_variant | 30/182 | 5 | NM_001164508.2 | ENSP00000380505.3 | ||
NEB | ENST00000427231.7 | c.2987T>C | p.Ile996Thr | missense_variant | 30/182 | 5 | NM_001164507.2 | ENSP00000416578.2 | ||
NEB | ENST00000409198.5 | c.2987T>C | p.Ile996Thr | missense_variant | 30/150 | 5 | ENSP00000386259.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249188Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135186
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461244Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 726924
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ExAC
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ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nemaline myopathy 2 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 06, 2022 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;.;.
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;M;M;M;M
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;N;N;.;.
REVEL
Benign
Sift
Benign
D;T;.;T;D;.;.
Sift4G
Pathogenic
D;D;D;D;D;D;D
Polyphen
0.94
.;.;.;.;P;.;.
Vest4
MutPred
Gain of disorder (P = 0.0235);Gain of disorder (P = 0.0235);Gain of disorder (P = 0.0235);Gain of disorder (P = 0.0235);Gain of disorder (P = 0.0235);Gain of disorder (P = 0.0235);Gain of disorder (P = 0.0235);
MVP
MPC
0.36
ClinPred
D
GERP RS
Varity_R
gMVP
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