14-96392259-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_152327.5(AK7):c.105G>A(p.Lys35Lys) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00000186 in 1,610,900 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 predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_152327.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AK7 | ENST00000267584.9 | c.105G>A | p.Lys35Lys | splice_region_variant, synonymous_variant | Exon 1 of 18 | 1 | NM_152327.5 | ENSP00000267584.4 | ||
AK7 | ENST00000555570.1 | c.105G>A | p.Lys35Lys | splice_region_variant, synonymous_variant | Exon 1 of 2 | 2 | ENSP00000451068.1 | |||
AK7 | ENST00000556643.1 | n.116G>A | splice_region_variant, non_coding_transcript_exon_variant | Exon 1 of 3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152246Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250162Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135468
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1458654Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725772
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152246Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74372
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change affects codon 35 of the AK7 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the AK7 protein. This variant also falls at the last nucleotide of exon 1, which is part of the consensus splice site for this exon. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AK7-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at