rs2832115

Positions:

• chr21-28849087-G-A

Variant summary

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

The XR_007067787.1(N6AMT1):​n.867+23526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,020 control chromosomes in the GnomAD database, including 6,584 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 0.27 (6584 hom., cov: 32)
• Consequence: N6AMT1 XR_007067787.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09

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=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
N6AMT1	XR_007067787.1	n.867+23526C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41152 AN: 151902 Hom.: 6576 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.271 AC: 41192 AN: 152020 Hom.: 6584 Cov.: 32 AF XY: 0.273 AC XY: 20306 AN XY: 74298

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.269

Alfa AF: 0.199 Hom.: 6196

Bravo AF: 0.276

Asia WGS AF: 0.317 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.36
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2832115; hg19: chr21-30221409;