chr1-77916110-AATG-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The NM_144573.4(NEXN):βc.7_9delβ(p.Asp3del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000149 in 1,607,658 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.000013 ( 0 hom., cov: 32)
Exomes π: 0.000015 ( 0 hom. )
Consequence
NEXN
NM_144573.4 inframe_deletion
NM_144573.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.37
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 -3 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_144573.4. Strenght limited to Supporting due to length of the change: 1aa.
BS2
High AC in GnomAdExome4 at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEXN | NM_144573.4 | c.7_9del | p.Asp3del | inframe_deletion | 2/13 | ENST00000334785.12 | NP_653174.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEXN | ENST00000334785.12 | c.7_9del | p.Asp3del | inframe_deletion | 2/13 | 1 | NM_144573.4 | ENSP00000333938 | P3 | |
NEXN | ENST00000401035.7 | c.7_9del | p.Asp3del | inframe_deletion | 2/9 | 1 | ENSP00000383814 | |||
NEXN | ENST00000330010.12 | c.7_9del | p.Asp3del | inframe_deletion | 2/12 | 2 | ENSP00000327363 | A1 | ||
NEXN | ENST00000440324.5 | c.7_9del | p.Asp3del | inframe_deletion | 2/10 | 5 | ENSP00000411902 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247444Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134230
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1455528Hom.: 0 AF XY: 0.0000110 AC XY: 8AN XY: 724164
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 25, 2023 | The c.7_9delGAT variant (also known as p.D3del) is located in coding exon 1 of the NEXN gene. This variant results from an in-frame GAT deletion at nucleotide positions 7 to 9. This results in the in-frame deletion of an aspartic acid at codon 3. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Dilated cardiomyopathy 1CC;C3151267:Hypertrophic cardiomyopathy 20 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 08, 2021 | This variant, c.7_9del, results in the deletion of 1 amino acid(s) of the NEXN protein (p.Asp3del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs760463744, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with NEXN-related conditions. ClinVar contains an entry for this variant (Variation ID: 518850). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at