rs727503344
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_144573.4(NEXN):c.1660-11_1660-7del variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0000242 in 1,611,374 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000066 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
NEXN
NM_144573.4 splice_polypyrimidine_tract, intron
NM_144573.4 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.76
Genes affected
NEXN (HGNC:29557): (nexilin F-actin binding protein) This gene encodes a filamentous actin-binding protein that may function in cell adhesion and migration. Mutations in this gene have been associated with dilated cardiomyopathy, also known as CMD1CC. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP6
?
Variant 1-77942445-ATTTAT-A is Benign according to our data. Variant chr1-77942445-ATTTAT-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 164795.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS2
?
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEXN | NM_144573.4 | c.1660-11_1660-7del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000334785.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEXN | ENST00000334785.12 | c.1660-11_1660-7del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_144573.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152150Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246910Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134332
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GnomAD4 exome AF: 0.0000199 AC: 29AN: 1459224Hom.: 0 AF XY: 0.0000207 AC XY: 15AN XY: 726028
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152150Hom.: 1 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74342
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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 | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 03, 2013 | The 1660-11_1660-7del variant in NEXN has not been reported in the literature no r previously identified by our laboratory. This variant has been identified in 2 /7824 European American chromosomes by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS/). This variant is located in the 3' splice region. Computational tools suggest a possible impact to splicing, though this informati on is not predictive enough to determine pathogenicity. Additional information i s needed to fully assess the clinical significance of this variant. - |
Dilated cardiomyopathy 1CC;C3151267:Hypertrophic cardiomyopathy 20 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 25, 2022 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at