21-28715445-T-G

Variant names:

• chr21-28715445-T-G
• rs2091966
• XR_007067787.1:n.936+106460A>C

Variant summary

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

The XR_007067787.1(N6AMT1):​n.936+106460A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,008 control chromosomes in the GnomAD database, including 23,911 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 0.54 (23911 hom., cov: 32)
• Consequence: N6AMT1 XR_007067787.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284

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 = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
N6AMT1	XR_007067787.1	n.936+106460A>C		intron_variant	Intron 8 of 8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81498 AN: 151890 Hom.: 23864 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.537 AC: 81596 AN: 152008 Hom.: 23911 Cov.: 32 AF XY: 0.538 AC XY: 39936 AN XY: 74284

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.542

Alfa AF: 0.488 Hom.: 2613

Bravo AF: 0.559

Asia WGS AF: 0.646 AC: 2244 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	1.9
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2091966; hg19: chr21-30087767;