rs8134601

Variant names:

• chr21-28807306-G-A
• rs8134601
• XR_007067787.1:n.936+14599C>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+14599C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,078 control chromosomes in the GnomAD database, including 2,354 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 0.11 (2354 hom., cov: 32)
• Consequence: N6AMT1 XR_007067787.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
N6AMT1	XR_007067787.1	n.936+14599C>T		intron_variant	Intron 8 of 8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16904 AN: 151960 Hom.: 2347 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00534

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.111 AC: 16937 AN: 152078 Hom.: 2354 Cov.: 32 AF XY: 0.111 AC XY: 8290 AN XY: 74352

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0542

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.0411

Gnomad4 FIN AF: 0.0297

Gnomad4 NFE AF: 0.00534

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0586 Hom.: 243

Bravo AF: 0.128

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.43
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8134601; hg19: chr21-30179629;