21-28879027-G-T

Position:

• chr21-28879027-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.397-694C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 146,190 control chromosomes in the GnomAD database, including 57,969 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 0.89 (57969 hom., cov: 28)
• Consequence: N6AMT1 NM_013240.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
N6AMT1	NM_013240.6	c.397-694C>A		intron_variant		ENST00000303775.10	NP_037372.4
N6AMT1	NM_182749.5	c.313-694C>A		intron_variant			NP_877426.4
N6AMT1	NR_047510.3	n.419-694C>A		intron_variant, non_coding_transcript_variant
N6AMT1	XR_007067787.1	n.419-694C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
N6AMT1	ENST00000303775.10	c.397-694C>A		intron_variant		1	NM_013240.6	ENSP00000303584	P1
N6AMT1	ENST00000351429.7	c.313-694C>A		intron_variant		1		ENSP00000286764
N6AMT1	ENST00000460212.1	c.397-694C>A		intron_variant, NMD_transcript_variant		1		ENSP00000436490

Frequencies

GnomAD3 genomes AF: 0.889 AC: 129921 AN: 146192 Hom.: 57964 Cov.: 28

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.822

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.889 AC: 129928 AN: 146190 Hom.: 57969 Cov.: 28 AF XY: 0.888 AC XY: 62973 AN XY: 70924

Gnomad4 AFR AF: 0.933

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.948

Gnomad4 FIN AF: 0.910

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.875

Alfa AF: 0.894 Hom.: 13539

Bravo AF: 0.879

Asia WGS AF: 0.817 AC: 2804 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.48
DANN	Benign	0.075

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: rs2705671; hg19: chr21-30251349;