dbSNP rs1442596171: NAT8L:p.Pro59Gln (chr4-2059687-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178557.4(NAT8L):c.176C>A(p.Pro59Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign 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. P59R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NAT8L
NM_178557.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.387

Publications

0 publications found

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]

NAT8L Gene-Disease associations (from GenCC):

N-acetylaspartate deficiency
Inheritance: AR, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

NAT8L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178557.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT8L	NM_178557.4	MANE Select	c.176C>A	p.Pro59Gln	missense	Exon 1 of 3	NP_848652.2	Q8N9F0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT8L	ENST00000423729.3	TSL:1 MANE Select	c.176C>A	p.Pro59Gln	missense	Exon 1 of 3	ENSP00000413064.2	Q8N9F0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

887288

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

415620

African (AFR)

AF:

0.00

AC:

AN:

16870

American (AMR)

AF:

0.00

AC:

AN:

2456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6704

East Asian (EAS)

AF:

0.00

AC:

AN:

8182

South Asian (SAS)

AF:

0.00

AC:

AN:

18016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1940

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

796530

Other (OTH)

AF:

0.00

AC:

AN:

30514

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.028

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.36

M_CAP

Benign

0.013

MetaRNN

Benign

0.085

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.39

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.22

REVEL

Benign

0.035

Sift

Benign

0.26

Sift4G

Benign

0.095

Vest4

0.11

MutPred

0.20

Loss of glycosylation at P56 (P = 0.0015)

MVP

0.23

MPC

0.86

ClinPred

0.11

GERP RS

2.4

PromoterAI

-0.10

Neutral

(source)

Varity_R

0.095

gMVP

0.39

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.25

Position offset: 1

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over