rs587777212

chr4-2059711-CGGGGGGCGCGGGGCCGCCG-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_178557.4(NAT8L):c.212_230del(p.Gly71AlafsTer55) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000106 in 939,296 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: NAT8L NM_178557.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.33

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-2059711-CGGGGGGCGCGGGGCCGCCG-C is Pathogenic according to our data. Variant chr4-2059711-CGGGGGGCGCGGGGCCGCCG-C is described in ClinVar as [Pathogenic]. Clinvar id is 30849.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT8L	NM_178557.4	c.212_230del	p.Gly71AlafsTer55	frameshift_variant	1/3	ENST00000423729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT8L	ENST00000423729.3	c.212_230del	p.Gly71AlafsTer55	frameshift_variant	1/3	1	NM_178557.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000106 AC: 1 AN: 939296 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 446944

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000121

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

N-acetylaspartate deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 14, 2009

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs587777212; hg19: chr4-2061438;