rs2205449

Positions:

• chr21-28879766-T-C
• chr21-28879766-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013240.6(N6AMT1):​c.396+104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 801,190 control chromosomes in the GnomAD database, including 1 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 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000099 (0 hom.)
• Consequence: N6AMT1 NM_013240.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
N6AMT1	NM_013240.6	c.396+104A>G		intron_variant		ENST00000303775.10	NP_037372.4
N6AMT1	NM_182749.5	c.313-1433A>G		intron_variant			NP_877426.4
N6AMT1	NR_047510.3	n.418+104A>G		intron_variant, non_coding_transcript_variant
N6AMT1	XR_007067787.1	n.418+104A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
N6AMT1	ENST00000303775.10	c.396+104A>G		intron_variant		1	NM_013240.6	ENSP00000303584	P1
N6AMT1	ENST00000351429.7	c.313-1433A>G		intron_variant		1		ENSP00000286764
N6AMT1	ENST00000460212.1	c.396+104A>G		intron_variant, NMD_transcript_variant		1		ENSP00000436490

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 168 AN: 151996 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00334

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.0000986 AC: 64 AN: 649076 Hom.: 0 AF XY: 0.0000899 AC XY: 30 AN XY: 333616

Gnomad4 AFR exome AF: 0.00282

Gnomad4 AMR exome AF: 0.000736

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000215

Gnomad4 OTH exome AF: 0.000387

GnomAD4 genome AF: 0.00110 AC: 168 AN: 152114 Hom.: 1 Cov.: 32 AF XY: 0.00105 AC XY: 78 AN XY: 74352

Gnomad4 AFR AF: 0.00333

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2205449; hg19: chr21-30252088;