rs779009256
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_057175.5(NAA15):c.239_240del(p.His80ArgfsTer17) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000316 in 1,583,634 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
NAA15
NM_057175.5 frameshift
NM_057175.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.95
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 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 4-139336946-CAT-C is Pathogenic according to our data. Variant chr4-139336946-CAT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 559844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NAA15 | NM_057175.5 | c.239_240del | p.His80ArgfsTer17 | frameshift_variant | 3/20 | ENST00000296543.10 | |
NAA15 | NM_001410842.1 | c.239_240del | p.His80ArgfsTer17 | frameshift_variant | 3/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAA15 | ENST00000296543.10 | c.239_240del | p.His80ArgfsTer17 | frameshift_variant | 3/20 | 1 | NM_057175.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152058Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
2
AN:
152058
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000429 AC: 1AN: 233146Hom.: 0 AF XY: 0.00000788 AC XY: 1AN XY: 126914
GnomAD3 exomes
AF:
AC:
1
AN:
233146
Hom.:
AF XY:
AC XY:
1
AN XY:
126914
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000210 AC: 3AN: 1431576Hom.: 0 AF XY: 0.00000421 AC XY: 3AN XY: 711938
GnomAD4 exome
AF:
AC:
3
AN:
1431576
Hom.:
AF XY:
AC XY:
3
AN XY:
711938
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152058Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74260
GnomAD4 genome
?
AF:
AC:
2
AN:
152058
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74260
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:13
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Intellectual disability, autosomal dominant 50 Pathogenic:6
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 30, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 07, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 05, 2018 | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. A portion of the reported individuals presented cardiovascular defects [PMID 28303347] - |
Pathogenic, criteria provided, single submitter | clinical testing | Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille | - | - - |
Pathogenic, no assertion criteria provided | clinical testing | Clinical Genetics Laboratory, University Hospital Schleswig-Holstein | Apr 05, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Daryl Scott Lab, Baylor College of Medicine | Apr 11, 2023 | - - |
not provided Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center | Dec 22, 2020 | PVS1, PM6_Strong - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Oct 23, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Oct 24, 2023 | Identified as an apparently de novo variant in a patient with diaphragmatic hernia in the published literature, but detailed clinical information was not provided (PMID: 28303347); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28191889, 29656860, 28303347, 34210367) - |
Global developmental delay Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Human Genetics Bochum, Ruhr University Bochum | Feb 16, 2022 | ACMG criteria used to clasify this variant: PVS1, PM6, PM2_SUP - |
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 29, 2017 | - - |
See cases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetics Laboratory, UDIAT-Centre Diagnòstic, Hospital Universitari Parc Tauli | Apr 26, 2021 | PVS1_very strong;PP5_strong;PM2_supporting;PM6_moderate - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at