8-18222931-A-G

Variant names:

• chr8-18222931-A-G
• rs55793712
• NM_000662.8:c.*11A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000662.8(NAT1):​c.*11A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,374,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: NAT1 NM_000662.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 6 publications found

Genes affected

NAT1 (HGNC:7645): (N-acetyltransferase 1) This gene is one of two arylamine N-acetyltransferase (NAT) genes in the human genome, and is orthologous to the mouse and rat Nat2 genes. The enzyme encoded by this gene catalyzes the transfer of an acetyl group from acetyl-CoA to various arylamine and hydrazine substrates. This enzyme helps metabolize drugs and other xenobiotics, and functions in folate catabolism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000662.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	NM_000662.8	MANE Select	c.*11A>G		3_prime_UTR	Exon 3 of 3	NP_000653.3
	NAT1	NM_001160175.4		c.*11A>G		3_prime_UTR	Exon 5 of 5	NP_001153647.1
	NAT1	NM_001160176.4		c.*11A>G		3_prime_UTR	Exon 4 of 4	NP_001153648.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	ENST00000307719.9	TSL:1 MANE Select	c.*11A>G		3_prime_UTR	Exon 3 of 3	ENSP00000307218.4
	NAT1	ENST00000518029.5	TSL:1	c.*11A>G		3_prime_UTR	Exon 4 of 4	ENSP00000428270.1
	NAT1	ENST00000545197.3	TSL:5	c.*11A>G		3_prime_UTR	Exon 4 of 4	ENSP00000443194.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000558 AC: 1 AN: 179238 AF XY: 0.0000105

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1374710 Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1 AN XY: 675936

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30604

American (AMR) AF: 0.00 AC: 0 AN: 29968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20590

East Asian (EAS) AF: 0.00 AC: 0 AN: 39034

South Asian (SAS) AF: 0.0000149 AC: 1 AN: 67114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5080

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075462

Other (OTH) AF: 0.00 AC: 0 AN: 56830

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000807 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.8
DANN	Benign	0.79
PhyloP100		-0.10

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: rs55793712; hg19: chr8-18080440;