rs2832053

Variant names:

• chr21-28758655-G-A
• rs2832053
• XR_007067787.1:n.936+63250C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007067787.1(N6AMT1):​n.936+63250C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,130 control chromosomes in the GnomAD database, including 1,832 homozygotes. 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: 𝑓 0.15 (1832 hom., cov: 32)
• Consequence: N6AMT1 XR_007067787.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375

Genes affected

N6AMT1 (HGNC:16021): (N-6 adenine-specific DNA methyltransferase 1) This gene encodes an N(6)-adenine-specific DNA methyltransferase. The encoded enzyme may be involved in the methylation of release factor I during translation termination. This enzyme is also involved in converting the arsenic metabolite monomethylarsonous acid to the less toxic dimethylarsonic acid. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Mar 2023]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
N6AMT1	XR_007067787.1	n.936+63250C>T		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22061 AN: 152012 Hom.: 1831 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.157

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.145 AC: 22061 AN: 152130 Hom.: 1832 Cov.: 32 AF XY: 0.152 AC XY: 11286 AN XY: 74380

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.157

Alfa AF: 0.135 Hom.: 194

Bravo AF: 0.140

Asia WGS AF: 0.258 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2832053; hg19: chr21-30130977;