11-63952522-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024771.4(NAA40):​c.367C>T​(p.His123Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,614,074 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00034 ( 1 hom. )

Consequence

NAA40
NM_024771.4 missense

Scores

3
12
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63
Variant links:
Genes affected
NAA40 (HGNC:25845): (N-alpha-acetyltransferase 40, NatD catalytic subunit) Enables H2A histone acetyltransferase activity; H4 histone acetyltransferase activity; and peptide-serine-N-acetyltransferase activity. Involved in N-terminal protein amino acid acetylation; histone H2A acetylation; and histone H4 acetylation. Located in centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAA40NM_024771.4 linkc.367C>T p.His123Tyr missense_variant Exon 5 of 8 ENST00000377793.9 NP_079047.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NAA40ENST00000377793.9 linkc.367C>T p.His123Tyr missense_variant Exon 5 of 8 1 NM_024771.4 ENSP00000367024.4 Q86UY6-1

Frequencies

GnomAD3 genomes
AF:
0.000191
AC:
29
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000338
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000211
AC:
53
AN:
251480
Hom.:
0
AF XY:
0.000213
AC XY:
29
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000405
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000290
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000345
AC:
504
AN:
1461894
Hom.:
1
Cov.:
32
AF XY:
0.000352
AC XY:
256
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000423
Gnomad4 OTH exome
AF:
0.000315
GnomAD4 genome
AF:
0.000191
AC:
29
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.000197
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000338
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000312
Hom.:
0
Bravo
AF:
0.000298
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000165
AC:
20
EpiCase
AF:
0.000273
EpiControl
AF:
0.000356

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.367C>T (p.H123Y) alteration is located in exon 5 (coding exon 5) of the NAA40 gene. This alteration results from a C to T substitution at nucleotide position 367, causing the histidine (H) at amino acid position 123 to be replaced by a tyrosine (Y). 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
0.96
BayesDel_addAF
Uncertain
0.023
T
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.032
D
MetaRNN
Pathogenic
0.77
D;D
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.5
M;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-4.7
D;D
REVEL
Uncertain
0.56
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.011
D;D
Polyphen
0.99
D;.
Vest4
0.94
MVP
0.54
MPC
1.3
ClinPred
0.68
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.85
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs201680695; hg19: chr11-63719994; API