rs1048546

Positions:

• chr21-28872555-G-T

Variant summary

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

The NM_013240.6(N6AMT1):​c.*3830C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,008 control chromosomes in the GnomAD database, including 8,710 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 0.33 (8709 hom., cov: 32)
  • Exomes 𝑓: 0.40 (1 hom.)
• Consequence: N6AMT1 NM_013240.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629

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 (Cadd=0.741).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
N6AMT1	NM_013240.6	c.*3830C>A		3_prime_UTR_variant	6/6	ENST00000303775.10	NP_037372.4
N6AMT1	NM_182749.5	c.*3830C>A		3_prime_UTR_variant	5/5		NP_877426.4
N6AMT1	NR_047510.3	n.925C>A		non_coding_transcript_exon_variant	7/7
N6AMT1	XR_007067787.1	n.867+58C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
N6AMT1	ENST00000303775.10	c.*3830C>A		3_prime_UTR_variant	6/6	1	NM_013240.6	ENSP00000303584	P1
N6AMT1	ENST00000351429.7	c.*3830C>A		3_prime_UTR_variant	5/5	1		ENSP00000286764
N6AMT1	ENST00000460212.1	c.*258C>A		3_prime_UTR_variant, NMD_transcript_variant	7/7	1		ENSP00000436490

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50693 AN: 151870 Hom.: 8700 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.400 AC: 8 AN: 20 Hom.: 1 Cov.: 0 AF XY: 0.313 AC XY: 5 AN XY: 16

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.429

GnomAD4 genome AF: 0.334 AC: 50729 AN: 151988 Hom.: 8709 Cov.: 32 AF XY: 0.336 AC XY: 24935 AN XY: 74266

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.354

Alfa AF: 0.307 Hom.: 14856

Bravo AF: 0.342

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1048546; hg19: -;