ENST00000430247.1:n.21-23567G>A

Variant names:

• chr21-28600947-C-T
• rs1236428
• ENST00000430247.1:n.21-23567G>A

Variant summary

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

The ENST00000430247.1(ENSG00000232855):​n.21-23567G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,222 control chromosomes in the GnomAD database, including 55,599 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 0.85 (55599 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000430247.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176

Genes affected

ENSG00000232855 (HGNC:58104):

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
N6AMT1	XR_007067787.1	n.937-23567G>A		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000232855	ENST00000430247.1	n.21-23567G>A		intron_variant	Intron 1 of 4	5
ENSG00000232855	ENST00000433310.6	n.295-23567G>A		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129463 AN: 152104 Hom.: 55536 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.842

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

GnomAD4 genome AF: 0.851 AC: 129583 AN: 152222 Hom.: 55599 Cov.: 32 AF XY: 0.852 AC XY: 63445 AN XY: 74436

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.883

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.794

Gnomad4 OTH AF: 0.840

Alfa AF: 0.821 Hom.: 25281

Bravo AF: 0.869

Asia WGS AF: 0.844 AC: 2937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.7
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1236428; hg19: chr21-29973269;