1-77916133-G-A
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.Glu9Glu) 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
Consequence
NM_144573.4 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEXN | ENST00000334785.12 | c.27G>A | p.Glu9Glu | splice_region_variant, synonymous_variant | Exon 2 of 13 | 1 | NM_144573.4 | ENSP00000333938.7 | ||
NEXN | ENST00000401035.7 | c.27G>A | p.Glu9Glu | splice_region_variant, synonymous_variant | Exon 2 of 9 | 1 | ENSP00000383814.3 | |||
NEXN | ENST00000330010.12 | c.27G>A | p.Glu9Glu | splice_region_variant, synonymous_variant | Exon 2 of 12 | 2 | ENSP00000327363.8 | |||
NEXN | ENST00000440324.5 | c.27G>A | p.Glu9Glu | splice_region_variant, synonymous_variant | Exon 2 of 10 | 5 | ENSP00000411902.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151880Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000344 AC: 5AN: 1451750Hom.: 0 Cov.: 28 AF XY: 0.00000277 AC XY: 2AN XY: 722176
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151880Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74162
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at