9-85958544-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_024635.4(NAA35):āc.231C>Gā(p.Asn77Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,852 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
NAA35
NM_024635.4 missense
NM_024635.4 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 0.863
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, NAA35
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NAA35 | NM_024635.4 | c.231C>G | p.Asn77Lys | missense_variant | 4/23 | ENST00000361671.10 | |
NAA35 | NM_001321881.2 | c.231C>G | p.Asn77Lys | missense_variant | 4/23 | ||
NAA35 | NM_001321882.2 | c.231C>G | p.Asn77Lys | missense_variant | 4/23 | ||
NAA35 | XM_005252127.5 | c.231C>G | p.Asn77Lys | missense_variant | 4/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAA35 | ENST00000361671.10 | c.231C>G | p.Asn77Lys | missense_variant | 4/23 | 1 | NM_024635.4 | P1 | |
NAA35 | ENST00000376040.2 | c.231C>G | p.Asn77Lys | missense_variant | 4/12 | 2 | |||
NAA35 | ENST00000416045.4 | n.328C>G | non_coding_transcript_exon_variant | 4/7 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1458852Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 725768
GnomAD4 exome
AF:
AC:
1
AN:
1458852
Hom.:
Cov.:
29
AF XY:
AC XY:
1
AN XY:
725768
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | Oct 28, 2022 | This variant has not been reported in the literature in individuals affected with NAA35-related conditions. 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 is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 77 of the NAA35 protein (p.Asn77Lys). 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Gain of methylation at N77 (P = 0.0044);Gain of methylation at N77 (P = 0.0044);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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