Variant 21-28885309-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013240.6(N6AMT1):c.37C>A(p.His13Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000252 in 1,588,030 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

N6AMT1
NM_013240.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.02

Variant links:

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]

N6AMT1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
N6AMT1	NM_013240.6 linkuse as main transcript	c.37C>A	p.His13Asn	missense_variant	1/6	ENST00000303775.10
N6AMT1	NM_182749.5 linkuse as main transcript	c.37C>A	p.His13Asn	missense_variant	1/5
N6AMT1	NR_047510.3 linkuse as main transcript	n.59C>A		non_coding_transcript_exon_variant	1/7
N6AMT1	XR_007067787.1 linkuse as main transcript	n.59C>A		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
N6AMT1	ENST00000303775.10 linkuse as main transcript	c.37C>A	p.His13Asn	missense_variant	1/6	1	NM_013240.6	P1	Q9Y5N5-1
N6AMT1	ENST00000351429.7 linkuse as main transcript	c.37C>A	p.His13Asn	missense_variant	1/5	1			Q9Y5N5-2
N6AMT1	ENST00000460212.1 linkuse as main transcript	c.37C>A	p.His13Asn	missense_variant, NMD_transcript_variant	1/7	1			Q9Y5N5-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1435810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.15e-7

Gnomad4 OTH exome

AF:

0.0000339

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 26, 2023

The c.37C>A (p.H13N) alteration is located in exon 1 (coding exon 1) of the N6AMT1 gene. This alteration results from a C to A substitution at nucleotide position 37, causing the histidine (H) at amino acid position 13 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

Cadd

Pathogenic

Dann

Benign

0.97

DEOGEN2

Uncertain

0.48

T;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.71

D;D

MetaSVM

Benign

-0.85

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Benign

0.22

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.97

D;D

Vest4

0.62

MutPred

0.44

Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);

MVP

0.57

MPC

0.61

ClinPred

1.0

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.82

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over