rs2205445

Positions:

• chr21-28824690-T-C

Variant summary

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

The XR_007067787.1(N6AMT1):​n.868-2717A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 152,272 control chromosomes in the GnomAD database, including 226 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 0.046 (226 hom., cov: 32)
• Consequence: N6AMT1 XR_007067787.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
N6AMT1	XR_007067787.1	n.868-2717A>G		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7052 AN: 152154 Hom.: 224 Cov.: 32

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0340

Gnomad OTH AF: 0.0487

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

GnomAD4 genome AF: 0.0464 AC: 7068 AN: 152272 Hom.: 226 Cov.: 32 AF XY: 0.0463 AC XY: 3449 AN XY: 74450

Gnomad4 AFR AF: 0.0577

Gnomad4 AMR AF: 0.0485

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.0402

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.0340

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0374 Hom.: 12

Bravo AF: 0.0515

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
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: rs2205445; hg19: chr21-30197012;