chr4-79325633-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_032693.3(NAA11):​c.245G>A​(p.Arg82Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NAA11
NM_032693.3 missense

Scores

9
8
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.38
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 made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.972

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAA11NM_032693.3 linkc.245G>A p.Arg82Gln 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.245G>A p.Arg82Gln missense_variant Exon 1 of 2 1 NM_032693.3 ENSP00000286794.4 Q9BSU3
NAA11ENST00000511542.1 linkn.-110G>A upstream_gene_variant 3 ENSP00000422022.1 H0Y8T0
NAA11ENST00000513733.1 linkn.-165G>A upstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461784
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 08, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.245G>A (p.R82Q) alteration is located in exon 1 (coding exon 1) of the NAA11 gene. This alteration results from a G to A substitution at nucleotide position 245, causing the arginine (R) at amino acid position 82 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.17
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.24
T
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.94
D
M_CAP
Uncertain
0.21
D
MetaRNN
Pathogenic
0.97
D
MetaSVM
Uncertain
-0.099
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-3.8
D
REVEL
Uncertain
0.50
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.81
MutPred
0.92
Gain of glycosylation at S80 (P = 0.0217);
MVP
0.69
MPC
0.75
ClinPred
1.0
D
GERP RS
5.2
Varity_R
0.68
gMVP
0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs371683505; hg19: chr4-80246787; API