1-77916133-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_144573.4(NEXN):c.27G>A(p.Glu9=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00000374 in 1,603,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
NEXN
NM_144573.4 splice_region, synonymous
NM_144573.4 splice_region, synonymous
Scores
2
Splicing: ADA: 0.8969
2
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 -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.21).
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEXN | NM_144573.4 | c.27G>A | p.Glu9= | splice_region_variant, synonymous_variant | 2/13 | ENST00000334785.12 | NP_653174.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEXN | ENST00000334785.12 | c.27G>A | p.Glu9= | splice_region_variant, synonymous_variant | 2/13 | 1 | NM_144573.4 | ENSP00000333938 | P3 | |
NEXN | ENST00000401035.7 | c.27G>A | p.Glu9= | splice_region_variant, synonymous_variant | 2/9 | 1 | ENSP00000383814 | |||
NEXN | ENST00000330010.12 | c.27G>A | p.Glu9= | splice_region_variant, synonymous_variant | 2/12 | 2 | ENSP00000327363 | A1 | ||
NEXN | ENST00000440324.5 | c.27G>A | p.Glu9= | splice_region_variant, synonymous_variant | 2/10 | 5 | ENSP00000411902 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151880Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000344 AC: 5AN: 1451750Hom.: 0 Cov.: 28 AF XY: 0.00000277 AC XY: 2AN XY: 722176
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151880Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74162
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2022 | The c.27G>A variant (also known as p.E9E), located in coding exon 1 of the NEXN gene. This variant results from a G to A substitution at nucleotide position 27. This nucleotide substitution does not change the glutamic acid at codon 9. However, this change occurs in the last base pair of coding exon 1, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at