rs1997605

Variant names:

• chr21-28885096-G-A
• rs1997605
• NM_013240.6:c.134+116C>T

Variant summary

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

The NM_013240.6(N6AMT1):​c.134+116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 1,371,842 control chromosomes in the GnomAD database, including 516,835 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 0.81 (50284 hom., cov: 31)
  • Exomes 𝑓: 0.87 (466551 hom.)
• Consequence: N6AMT1 NM_013240.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.748

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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
N6AMT1	NM_013240.6	c.134+116C>T		intron_variant	Intron 1 of 5	ENST00000303775.10	NP_037372.4
N6AMT1	NM_182749.5	c.134+116C>T		intron_variant	Intron 1 of 4		NP_877426.4
N6AMT1	NR_047510.3	n.156+116C>T		intron_variant	Intron 1 of 6
N6AMT1	XR_007067787.1	n.156+116C>T		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
N6AMT1	ENST00000303775.10	c.134+116C>T		intron_variant	Intron 1 of 5	1	NM_013240.6	ENSP00000303584.5
N6AMT1	ENST00000351429.7	c.134+116C>T		intron_variant	Intron 1 of 4	1		ENSP00000286764.4
N6AMT1	ENST00000460212.1	n.134+116C>T		intron_variant	Intron 1 of 6	1		ENSP00000436490.1

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122584 AN: 151968 Hom.: 50262 Cov.: 31

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.819

GnomAD4 exome AF: 0.871 AC: 1062092 AN: 1219756 Hom.: 466551 AF XY: 0.873 AC XY: 518985 AN XY: 594484

Gnomad4 AFR exome AF: 0.685

Gnomad4 AMR exome AF: 0.709

Gnomad4 ASJ exome AF: 0.884

Gnomad4 EAS exome AF: 0.469

Gnomad4 SAS exome AF: 0.943

Gnomad4 FIN exome AF: 0.917

Gnomad4 NFE exome AF: 0.887

Gnomad4 OTH exome AF: 0.864

GnomAD4 genome AF: 0.807 AC: 122661 AN: 152086 Hom.: 50284 Cov.: 31 AF XY: 0.807 AC XY: 60054 AN XY: 74382

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.881

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.926

Gnomad4 FIN AF: 0.909

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.818

Alfa AF: 0.863 Hom.: 25918

Bravo AF: 0.784

Asia WGS AF: 0.727 AC: 2531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.6
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1997605; hg19: chr21-30257418; COSMIC: COSV58134580; COSMIC: COSV58134580;