dbSNP rs1345079759: NAT8L:p.Pro41Gln (chr4-2059633-C-A) – 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>A(p.Pro41Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000121 in 829,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P41L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

NAT8L
NM_178557.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.17567772).

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>A	p.Pro41Gln	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>A	p.Pro41Gln	missense	Exon 1 of 3	ENSP00000413064.2	Q8N9F0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000121

AC:

AN:

829238

Hom.:

Cov.:

AF XY:

0.00000261

AC XY:

AN XY:

383282

show subpopulations

African (AFR)

AF:

0.0000639

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.038

Eigen

Benign

-0.099

Eigen_PC

Benign

-0.086

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.40

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

PhyloP100

5.9

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.65

REVEL

Benign

0.040

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.013

Vest4

0.11

MutPred

0.19

Loss of glycosylation at P41 (P = 0.0092)

MVP

0.53

MPC

0.86

ClinPred

0.34

GERP RS

2.4

PromoterAI

0.0044

Neutral

(source)

Varity_R

0.10

gMVP

0.39

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over