Variant 4-2059607-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_178557.4(NAT8L):c.96C>T(p.Leu32Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 979,798 control chromosomes in the GnomAD database, including 351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.024 ( 113 hom., cov: 31)

Exomes 𝑓: 0.022 ( 238 hom. )

Consequence

NAT8L
NM_178557.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.316

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 4-2059607-C-T is Benign according to our data. Variant chr4-2059607-C-T is described in ClinVar as [Benign]. Clinvar id is 3060891.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.316 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT8L	NM_178557.4 linkuse as main transcript	c.96C>T	p.Leu32Leu	synonymous_variant	1/3	ENST00000423729.3	NP_848652.2	Q8N9F0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT8L	ENST00000423729.3 linkuse as main transcript	c.96C>T	p.Leu32Leu	synonymous_variant	1/3	1	NM_178557.4	ENSP00000413064.2		Q8N9F0

Frequencies

GnomAD3 genomes

AF:

0.0236

AC:

3412

AN:

144300

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00360

Gnomad AMI

AF:

0.00226

Gnomad AMR

AF:

0.0255

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.0722

Gnomad MID

AF:

0.00658

Gnomad NFE

AF:

0.0211

Gnomad OTH

AF:

0.0246

GnomAD3 exomes

AF:

0.0325

AC:

AN:

986

Hom.:

AF XY:

0.0367

AC XY:

AN XY:

626

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0270

Gnomad EAS exome

AF:

0.400

Gnomad SAS exome

AF:

0.0106

Gnomad FIN exome

AF:

0.0513

Gnomad NFE exome

AF:

0.0341

Gnomad OTH exome

AF:

0.0385

GnomAD4 exome

AF:

0.0217

AC:

18088

AN:

835396

Hom.:

238

Cov.:

AF XY:

0.0215

AC XY:

8307

AN XY:

386152

show subpopulations

Gnomad4 AFR exome

AF:

0.00177

Gnomad4 AMR exome

AF:

0.0287

Gnomad4 ASJ exome

AF:

0.0182

Gnomad4 EAS exome

AF:

0.158

Gnomad4 SAS exome

AF:

0.0107

Gnomad4 FIN exome

AF:

0.0594

Gnomad4 NFE exome

AF:

0.0215

Gnomad4 OTH exome

AF:

0.0266

GnomAD4 genome

AF:

0.0238

AC:

3437

AN:

144402

Hom.:

113

Cov.:

AF XY:

0.0257

AC XY:

1808

AN XY:

70226

show subpopulations

Gnomad4 AFR

AF:

0.00359

Gnomad4 AMR

AF:

0.0258

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.157

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.0722

Gnomad4 NFE

AF:

0.0211

Gnomad4 OTH

AF:

0.0347

Alfa

AF:

0.0241

Hom.:

Bravo

AF:

0.0217

Asia WGS

AF:

0.0730

AC:

131

AN:

1810

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NAT8L-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.93

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over