9-85942163-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_024635.4(NAA35):c.4G>A(p.Val2Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000278 in 1,613,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00029 ( 0 hom. )
Consequence
NAA35
NM_024635.4 missense
NM_024635.4 missense
Scores
2
5
12
Clinical Significance
Conservation
PhyloP100: 7.78
Genes affected
NAA35 (HGNC:24340): (N-alpha-acetyltransferase 35, NatC auxiliary subunit) Involved in negative regulation of apoptotic process. Located in cytosol; nucleoplasm; and plasma membrane. Part of NatC complex. Colocalizes with polysome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP2
Missense variant where missense usually causes diseases, NAA35
BP4
Computational evidence support a benign effect (MetaRNN=0.36047643).
BS2
High AC in GnomAd4 at 25 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NAA35 | NM_024635.4 | c.4G>A | p.Val2Ile | missense_variant | 2/23 | ENST00000361671.10 | |
NAA35 | NM_001321881.2 | c.4G>A | p.Val2Ile | missense_variant | 2/23 | ||
NAA35 | NM_001321882.2 | c.4G>A | p.Val2Ile | missense_variant | 2/23 | ||
NAA35 | XM_005252127.5 | c.4G>A | p.Val2Ile | missense_variant | 2/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAA35 | ENST00000361671.10 | c.4G>A | p.Val2Ile | missense_variant | 2/23 | 1 | NM_024635.4 | P1 | |
NAA35 | ENST00000376040.2 | c.4G>A | p.Val2Ile | missense_variant | 2/12 | 2 | |||
NAA35 | ENST00000416045.4 | n.101G>A | non_coding_transcript_exon_variant | 2/7 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152146Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000112 AC: 28AN: 250948Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135640
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GnomAD4 exome AF: 0.000289 AC: 423AN: 1461398Hom.: 0 Cov.: 30 AF XY: 0.000294 AC XY: 214AN XY: 726986
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GnomAD4 genome AF: 0.000164 AC: 25AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74458
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2 of the NAA35 protein (p.Val2Ile). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with NAA35-related conditions. This variant is present in population databases (rs201727123, gnomAD 0.02%). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at