4-79325642-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_032693.3(NAA11):​c.236G>C​(p.Arg79Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R79H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NAA11
NM_032693.3 missense

Scores

5
9
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.38

Publications

1 publications found
Variant links:
Genes affected
NAA11 (HGNC:28125): (N-alpha-acetyltransferase 11, NatA catalytic subunit) Enables peptide alpha-N-acetyltransferase activity. Involved in N-terminal protein amino acid acetylation. Located in several cellular components, including Golgi apparatus; centrosome; and nucleoplasm. Part of NatA complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.776

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAA11NM_032693.3 linkc.236G>C p.Arg79Pro missense_variant Exon 1 of 2 ENST00000286794.5 NP_116082.1 Q9BSU3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NAA11ENST00000286794.5 linkc.236G>C p.Arg79Pro missense_variant Exon 1 of 2 1 NM_032693.3 ENSP00000286794.4 Q9BSU3
NAA11ENST00000511542.1 linkn.-119G>C upstream_gene_variant 3 ENSP00000422022.1 H0Y8T0
NAA11ENST00000513733.1 linkn.-174G>C upstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000400
AC:
1
AN:
249704
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000550
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461788
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727182
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111932
Other (OTH)
AF:
0.00
AC:
0
AN:
60384
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.96
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.043
D
MetaRNN
Pathogenic
0.78
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.035
N
PhyloP100
7.4
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-6.8
D
REVEL
Uncertain
0.44
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.023
D
Polyphen
0.75
P
Vest4
0.89
MutPred
0.56
Loss of MoRF binding (P = 0.0085);
MVP
0.47
MPC
0.72
ClinPred
1.0
D
GERP RS
5.2
PromoterAI
-0.0033
Neutral
Varity_R
0.92
gMVP
0.57
Mutation Taster
=58/42
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs773548251; hg19: chr4-80246796; COSMIC: COSV99727608; COSMIC: COSV99727608; API