21-28879766-T-A

Position:

• chr21-28879766-T-A

Variant summary

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

The NM_013240.6(N6AMT1):​c.396+104A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 799,054 control chromosomes in the GnomAD database, including 139,608 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 0.49 (20353 hom., cov: 32)
  • Exomes 𝑓: 0.60 (119255 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
N6AMT1	NM_013240.6	c.396+104A>T		intron_variant		ENST00000303775.10	NP_037372.4
N6AMT1	NM_182749.5	c.313-1433A>T		intron_variant			NP_877426.4
N6AMT1	NR_047510.3	n.418+104A>T		intron_variant, non_coding_transcript_variant
N6AMT1	XR_007067787.1	n.418+104A>T		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>T		intron_variant		1	NM_013240.6	ENSP00000303584	P1
N6AMT1	ENST00000351429.7	c.313-1433A>T		intron_variant		1		ENSP00000286764
N6AMT1	ENST00000460212.1	c.396+104A>T		intron_variant, NMD_transcript_variant		1		ENSP00000436490

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73878 AN: 151918 Hom.: 20349 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.597 AC: 386497 AN: 647018 Hom.: 119255 AF XY: 0.599 AC XY: 199259 AN XY: 332572

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.450

Gnomad4 ASJ exome AF: 0.625

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.621

Gnomad4 FIN exome AF: 0.670

Gnomad4 NFE exome AF: 0.627

Gnomad4 OTH exome AF: 0.569

GnomAD4 genome AF: 0.486 AC: 73891 AN: 152036 Hom.: 20353 Cov.: 32 AF XY: 0.488 AC XY: 36246 AN XY: 74312

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.489

Alfa AF: 0.408 Hom.: 1282

Bravo AF: 0.461

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.0
DANN	Benign	0.51

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;