NM_178557.4:c.110C>T

Variant names:

• chr4-2059621-C-T
• rs934583303
• NM_178557.4:c.110C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_178557.4(NAT8L):​c.110C>T​(p.Ala37Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 978,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: NAT8L NM_178557.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.358
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0946919).

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.110C>T	p.Ala37Val	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.110C>T	p.Ala37Val	missense	Exon 1 of 3	ENSP00000413064.2	Q8N9F0

Frequencies

GnomAD3 genomes AF: 0.0000207 AC: 3 AN: 145230 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000628

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000840 AC: 7 AN: 833158 Hom.: 0 Cov.: 23 AF XY: 0.0000130 AC XY: 5 AN XY: 385024

African (AFR) AF: 0.00 AC: 0 AN: 15770

American (AMR) AF: 0.00 AC: 0 AN: 1042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5190

East Asian (EAS) AF: 0.00 AC: 0 AN: 3638

South Asian (SAS) AF: 0.000346 AC: 6 AN: 17350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 332

Middle Eastern (MID) AF: 0.000556 AC: 1 AN: 1798

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 760736

Other (OTH) AF: 0.00 AC: 0 AN: 27302

GnomAD4 genome AF: 0.0000207 AC: 3 AN: 145230 Hom.: 0 Cov.: 31 AF XY: 0.0000425 AC XY: 3 AN XY: 70578

African (AFR) AF: 0.00 AC: 0 AN: 40524

American (AMR) AF: 0.00 AC: 0 AN: 14662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3376

East Asian (EAS) AF: 0.00 AC: 0 AN: 4978

South Asian (SAS) AF: 0.000628 AC: 3 AN: 4776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65468

Other (OTH) AF: 0.00 AC: 0 AN: 2000

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.36
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.023
Sift	Benign	0.20	T
Sift4G	Benign	0.26	T
Vest4		0.061
MutPred		0.18		Loss of glycosylation at P41 (P = 0.0092)
MVP		0.44
MPC		0.92
ClinPred		0.085	T
GERP RS		1.3
PromoterAI		0.014	Neutral
Varity_R		0.066
gMVP		0.25
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs934583303; hg19: chr4-2061348;