4-2059687-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178557.4(NAT8L):​c.176C>T​(p.Pro59Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000097 in 1,031,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

NAT8L
NM_178557.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.387
Variant links:
Genes affected
NAT8L (HGNC:26742): (N-acetyltransferase 8 like) This gene encodes a single-pass membrane protein, which contains a conserved sequence of the GCN5 or NAT superfamily of N-acetyltransferases and is a member of the N-acyltransferase (NAT) superfamily. This protein is a neuron-specific protein and is the N-acetylaspartate (NAA) biosynthetic enzyme, catalyzing the NAA synthesis from L-aspartate and acetyl-CoA. NAA is a major storage and transport form of acetyl coenzyme A specific to the nervous system. The gene mutation results in primary NAA deficiency (hypoacetylaspartia). [provided by RefSeq, Dec 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08632347).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NAT8LNM_178557.4 linkc.176C>T p.Pro59Leu missense_variant 1/3 ENST00000423729.3 NP_848652.2 Q8N9F0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NAT8LENST00000423729.3 linkc.176C>T p.Pro59Leu missense_variant 1/31 NM_178557.4 ENSP00000413064.2 Q8N9F0

Frequencies

GnomAD3 genomes
AF:
0.0000139
AC:
2
AN:
143846
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000218
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000153
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000902
AC:
8
AN:
887288
Hom.:
0
Cov.:
21
AF XY:
0.00000722
AC XY:
3
AN XY:
415620
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000122
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000879
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000139
AC:
2
AN:
143846
Hom.:
0
Cov.:
32
AF XY:
0.0000286
AC XY:
2
AN XY:
70016
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000218
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000153
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 06, 2023The c.176C>T (p.P59L) alteration is located in exon 1 (coding exon 1) of the NAT8L gene. This alteration results from a C to T substitution at nucleotide position 176, causing the proline (P) at amino acid position 59 to be replaced by a leucine (L). 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
Benign
0.14
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
17
DANN
Benign
0.92
DEOGEN2
Benign
0.028
T
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.49
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.086
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-0.14
N
REVEL
Benign
0.029
Sift
Benign
0.11
T
Sift4G
Uncertain
0.034
D
Vest4
0.12
MutPred
0.26
Loss of glycosylation at P56 (P = 0.0015);
MVP
0.23
MPC
0.94
ClinPred
0.16
T
GERP RS
2.4
Varity_R
0.075
gMVP
0.37

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: rs1442596171; hg19: chr4-2061414; API