rs139610204
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The ENST00000377122.9(NEBL):āc.908A>Gā(p.Glu303Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000622 in 1,607,860 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: š 0.00038 ( 0 hom., cov: 32)
Exomes š: 0.000029 ( 0 hom. )
Consequence
NEBL
ENST00000377122.9 missense
ENST00000377122.9 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 2.21
Genes affected
NEBL (HGNC:16932): (nebulette) This gene encodes a nebulin like protein that is abundantly expressed in cardiac muscle. The encoded protein binds actin and interacts with thin filaments and Z-line associated proteins in striated muscle. This protein may be involved in cardiac myofibril assembly. A shorter isoform of this protein termed LIM nebulette is expressed in non-muscle cells and may function as a component of focal adhesion complexes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.045807213).
BP6
Variant 10-20852645-T-C is Benign according to our data. Variant chr10-20852645-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 454278.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEBL | NM_006393.3 | c.908A>G | p.Glu303Gly | missense_variant | 10/28 | ENST00000377122.9 | NP_006384.1 | |
LOC102725112 | XR_007062082.1 | n.223+4119T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.908A>G | p.Glu303Gly | missense_variant | 10/28 | 1 | NM_006393.3 | ENSP00000366326 |
Frequencies
GnomAD3 genomes AF: 0.000381 AC: 58AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000880 AC: 22AN: 250118Hom.: 0 AF XY: 0.0000740 AC XY: 10AN XY: 135184
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GnomAD4 exome AF: 0.0000289 AC: 42AN: 1455580Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18AN XY: 724504
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GnomAD4 genome AF: 0.000381 AC: 58AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74466
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 03, 2024 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868) - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Primary dilated cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 13, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
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