rs750276279
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_001164507.2(NEB):c.2062C>T(p.Pro688Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P688A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
NEB
NM_001164507.2 missense
NM_001164507.2 missense
Scores
11
7
Clinical Significance
Conservation
PhyloP100: 4.64
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 2-151692103-G-A is Benign according to our data. Variant chr2-151692103-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 465541.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.2062C>T | p.Pro688Ser | missense_variant | 22/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.2062C>T | p.Pro688Ser | missense_variant | 22/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.2062C>T | p.Pro688Ser | missense_variant | 22/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.2062C>T | p.Pro688Ser | missense_variant | 22/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000489048.1 | n.961C>T | non_coding_transcript_exon_variant | 10/12 | 1 | ||||
NEB | ENST00000409198.5 | c.2062C>T | p.Pro688Ser | missense_variant | 22/150 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249040Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135094
GnomAD3 exomes
AF:
AC:
8
AN:
249040
Hom.:
AF XY:
AC XY:
7
AN XY:
135094
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461664Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727114
GnomAD4 exome
AF:
AC:
19
AN:
1461664
Hom.:
Cov.:
31
AF XY:
AC XY:
15
AN XY:
727114
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
AF:
AC:
6
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
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;.;.
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;M;M;M;M
MutationTaster
Benign
D;D;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.;D;D;.;.
REVEL
Benign
Sift
Benign
T;T;.;T;T;.;.
Sift4G
Uncertain
D;D;D;D;D;D;D
Polyphen
0.98
.;.;.;.;D;.;.
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);
MVP
MPC
0.34
ClinPred
T
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