4-139334257-A-AGG
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_057175.5(NAA15):c.139_139+1dup variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
NAA15
NM_057175.5 frameshift, splice_region
NM_057175.5 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.60
Genes affected
NAA15 (HGNC:30782): (N-alpha-acetyltransferase 15, NatA auxiliary subunit) N-alpha-acetylation is among the most common post-translational protein modifications in eukaryotic cells. This process involves the transfer of an acetyl group from acetyl-coenzyme A to the alpha-amino group on a nascent polypeptide and is essential for normal cell function. This gene encodes the auxillary subunit of the N-terminal acetyltransferase A (NatA) complex. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 4-139334257-A-AGG is Pathogenic according to our data. Variant chr4-139334257-A-AGG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1709505.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NAA15 | NM_057175.5 | c.139_139+1dup | frameshift_variant, splice_region_variant | 2/20 | ENST00000296543.10 | ||
NAA15 | NM_001410842.1 | c.139_139+1dup | frameshift_variant, splice_region_variant | 2/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAA15 | ENST00000296543.10 | c.139_139+1dup | frameshift_variant, splice_region_variant | 2/20 | 1 | NM_057175.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 27
GnomAD4 exome
Cov.:
27
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability, autosomal dominant 50 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | MGZ Medical Genetics Center | Jul 26, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.