chr10-20826482-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_006393.3(NEBL):c.1834G>A(p.Glu612Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,612,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
NEBL
NM_006393.3 missense
NM_006393.3 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 3.44
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 10-20826482-C-T is Benign according to our data. Variant chr10-20826482-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 454265.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEBL | NM_006393.3 | c.1834G>A | p.Glu612Lys | missense_variant | 18/28 | ENST00000377122.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEBL | ENST00000377122.9 | c.1834G>A | p.Glu612Lys | missense_variant | 18/28 | 1 | NM_006393.3 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152156Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000678 AC: 17AN: 250746Hom.: 0 AF XY: 0.0000886 AC XY: 12AN XY: 135508
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GnomAD4 exome AF: 0.0000301 AC: 44AN: 1460666Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25AN XY: 726726
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74336
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 19, 2022 | The c.1834G>A (p.E612K) alteration is located in exon 18 (coding exon 18) of the NEBL gene. This alteration results from a G to A substitution at nucleotide position 1834, causing the glutamic acid (E) at amino acid position 612 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Primary dilated cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 18, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.0031);
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