Genetic Variant NAT8L:p.Pro41Leu (chr4-2059633-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178557.4(NAT8L):c.122C>T(p.Pro41Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000689 in 145,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NAT8L
NM_178557.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.91

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17155069).

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.122C>T	p.Pro41Leu	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.122C>T	p.Pro41Leu	missense	Exon 1 of 3	ENSP00000413064.2	Q8N9F0

Frequencies

GnomAD3 genomes

AF:

0.00000689

AC:

AN:

145122

Hom.:

Cov.:

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:

0.000201

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

829238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

383282

African (AFR)

AF:

0.00

AC:

AN:

15654

American (AMR)

AF:

0.00

AC:

AN:

1010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5136

East Asian (EAS)

AF:

0.00

AC:

AN:

3608

South Asian (SAS)

AF:

0.00

AC:

AN:

17226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1652

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

757492

Other (OTH)

AF:

0.00

AC:

AN:

27158

GnomAD4 genome

AF:

0.00000689

AC:

AN:

145122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70536

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40510

American (AMR)

AF:

0.00

AC:

AN:

14662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3378

East Asian (EAS)

AF:

0.000201

AC:

AN:

4980

South Asian (SAS)

AF:

0.00

AC:

AN:

4768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

298

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65402

Other (OTH)

AF:

0.00

AC:

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.050

Eigen

Benign

-0.063

Eigen_PC

Benign

-0.056

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.53

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

5.9

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.59

REVEL

Benign

0.052

Sift

Uncertain

0.010

Sift4G

Uncertain

0.016

Vest4

0.13

MutPred

0.22

Loss of glycosylation at P41 (P = 0.0092)

MVP

0.44

MPC

0.94

ClinPred

0.41

GERP RS

2.4

PromoterAI

0.018

Neutral

(source)

Varity_R

0.086

gMVP

0.40

Mutation Taster

=78/22

polymorphism

(source)

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

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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