rs368719373
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_001164507.2(NEB):c.10269G>A(p.Pro3423=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00098 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
NEB
NM_001164507.2 synonymous
NM_001164507.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.22
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 Benign. Variant got -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 2-151627080-C-T is Benign according to our data. Variant chr2-151627080-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 465429.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=1}.
BP7
Synonymous conserved (PhyloP=-3.22 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000979 (149/152188) while in subpopulation AFR AF= 0.00335 (139/41528). AF 95% confidence interval is 0.00289. There are 0 homozygotes in gnomad4. There are 68 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| NEB | NM_001164507.2 | c.10269G>A | p.Pro3423= | synonymous_variant | 70/182 | ENST00000427231.7 | |
| NEB | NM_001164508.2 | c.10269G>A | p.Pro3423= | synonymous_variant | 70/182 | ENST00000397345.8 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NEB | ENST00000397345.8 | c.10269G>A | p.Pro3423= | synonymous_variant | 70/182 | 5 | NM_001164508.2 | P5 | |
| NEB | ENST00000427231.7 | c.10269G>A | p.Pro3423= | synonymous_variant | 70/182 | 5 | NM_001164507.2 | A2 | |
| NEB | ENST00000409198.5 | c.9540G>A | p.Pro3180= | synonymous_variant | 67/150 | 5 |
Frequencies
GnomAD3 genomes 0.000980 AC: 149AN: 152070Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
149
AN:
152070
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000209 AC: 52AN: 249206Hom.: 0 AF XY: 0.000207 AC XY: 28AN XY: 135190
GnomAD3 exomes
AF:
AC:
52
AN:
249206
Hom.:
AF XY:
AC XY:
28
AN XY:
135190
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: 0.000113 AC: 165AN: 1461682Hom.: 0 Cov.: 31 AF XY: 0.000117 AC XY: 85AN XY: 727124
GnomAD4 exome
AF:
AC:
165
AN:
1461682
Hom.:
Cov.:
31
AF XY:
AC XY:
85
AN XY:
727124
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 0.000979 AC: 149AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.000914 AC XY: 68AN XY: 74412
GnomAD4 genome
AF:
AC:
149
AN:
152188
Hom.:
Cov.:
32
AF XY:
AC XY:
68
AN XY:
74412
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 04, 2020 | - - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 04, 2023 | - - |
NEB-related disorder Benign:1
| Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 15, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Nemaline myopathy 2 Benign:1
| Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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