chr4-2059576-C-T

Variant names:

• chr4-2059576-C-T
• rs1729810727
• NM_178557.4:c.65C>T

Variant summary

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

The NM_178557.4(NAT8L):​c.65C>T​(p.Ala22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NAT8L NM_178557.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.65C>T	p.Ala22Val	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.65C>T	p.Ala22Val	missense	Exon 1 of 3	ENSP00000413064.2	Q8N9F0

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 144858 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: 0.00

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: 0 AN: 848348 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 394344

African (AFR) AF: 0.00 AC: 0 AN: 16024

American (AMR) AF: 0.00 AC: 0 AN: 1748

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6146

East Asian (EAS) AF: 0.00 AC: 0 AN: 3838

South Asian (SAS) AF: 0.00 AC: 0 AN: 19868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2738

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 768886

Other (OTH) AF: 0.00 AC: 0 AN: 27994

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 144956 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 70474

African (AFR) AF: 0.00 AC: 0 AN: 40424

American (AMR) AF: 0.00 AC: 0 AN: 14684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3372

East Asian (EAS) AF: 0.00 AC: 0 AN: 4912

South Asian (SAS) AF: 0.00 AC: 0 AN: 4762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65364

Other (OTH) AF: 0.00 AC: 0 AN: 2008

Alfa AF: 0.00 Hom.: 0

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	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.8
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.029
Sift	Uncertain	0.012	D
Sift4G	Benign	0.17	T
Vest4		0.086
MutPred		0.17		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.58
MPC		0.92
ClinPred		0.28	T
GERP RS		2.4
PromoterAI		0.019	Neutral
Varity_R		0.12
gMVP		0.40
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.33		Position offset: -2

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

Other links and lift over

dbSNP: rs1729810727; hg19: chr4-2061303;