NM_001164507.2:c.12369C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001164507.2(NEB):​c.12369C>T​(p.Ile4123Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 4)
Exomes 𝑓: 0.000015 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NEB
NM_001164507.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -1.32

Publications

0 publications found
Variant links:
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]
NEB Gene-Disease associations (from GenCC):
  • nemaline myopathy 2
    Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P, Ambry Genetics
  • childhood-onset nemaline myopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • intermediate nemaline myopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • typical nemaline myopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • lethal multiple pterygium syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • severe congenital nemaline myopathy
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 2-151608638-G-A is Benign according to our data. Variant chr2-151608638-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 704472.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.32 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEBNM_001164507.2 linkc.12369C>T p.Ile4123Ile synonymous_variant Exon 82 of 182 ENST00000427231.7 NP_001157979.2
NEBNM_001164508.2 linkc.12369C>T p.Ile4123Ile synonymous_variant Exon 82 of 182 ENST00000397345.8 NP_001157980.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEBENST00000397345.8 linkc.12369C>T p.Ile4123Ile synonymous_variant Exon 82 of 182 5 NM_001164508.2 ENSP00000380505.3 P20929-2
NEBENST00000427231.7 linkc.12369C>T p.Ile4123Ile synonymous_variant Exon 82 of 182 5 NM_001164507.2 ENSP00000416578.2 P20929-3
NEBENST00000409198.5 linkc.11601+1171C>T intron_variant Intron 78 of 149 5 ENSP00000386259.1 P20929-4

Frequencies

GnomAD3 genomes
Cov.:
4
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000146
AC:
1
AN:
68514
Hom.:
0
Cov.:
0
AF XY:
0.0000285
AC XY:
1
AN XY:
35100
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
3722
American (AMR)
AF:
0.00
AC:
0
AN:
3852
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2996
East Asian (EAS)
AF:
0.00
AC:
0
AN:
6588
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2932
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
2634
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
342
European-Non Finnish (NFE)
AF:
0.0000245
AC:
1
AN:
40854
Other (OTH)
AF:
0.00
AC:
0
AN:
4594
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.825
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
4
Alfa
AF:
0.00
Hom.:
0

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
Jan 13, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Feb 13, 2020
Natera, Inc.
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
1.5
DANN
Benign
0.79
PhyloP100
-1.3
Mutation Taster
=98/2
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1277282343; hg19: chr2-152465152; API