Variant 21-28885233-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013240.6(N6AMT1):c.113C>A(p.Ala38Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,586,302 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

N6AMT1
NM_013240.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.511

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012435645).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
N6AMT1	NM_013240.6 linkuse as main transcript	c.113C>A	p.Ala38Glu	missense_variant	1/6	ENST00000303775.10	NP_037372.4
N6AMT1	NM_182749.5 linkuse as main transcript	c.113C>A	p.Ala38Glu	missense_variant	1/5		NP_877426.4
N6AMT1	NR_047510.3 linkuse as main transcript	n.135C>A		non_coding_transcript_exon_variant	1/7
N6AMT1	XR_007067787.1 linkuse as main transcript	n.135C>A		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
N6AMT1	ENST00000303775.10 linkuse as main transcript	c.113C>A	p.Ala38Glu	missense_variant	1/6	1	NM_013240.6	ENSP00000303584	P1	Q9Y5N5-1
N6AMT1	ENST00000351429.7 linkuse as main transcript	c.113C>A	p.Ala38Glu	missense_variant	1/5	1		ENSP00000286764		Q9Y5N5-2
N6AMT1	ENST00000460212.1 linkuse as main transcript	c.113C>A	p.Ala38Glu	missense_variant, NMD_transcript_variant	1/7	1		ENSP00000436490		Q9Y5N5-1

Frequencies

GnomAD3 genomes

AF:

0.000611

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00110

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000646

AC:

155

AN:

239982

Hom.:

AF XY:

0.000681

AC XY:

AN XY:

130666

show subpopulations

Gnomad AFR exome

AF:

0.000402

Gnomad AMR exome

AF:

0.000248

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.00104

GnomAD4 exome

AF:

0.00121

AC:

1742

AN:

1433964

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

816

AN XY:

710320

show subpopulations

Gnomad4 AFR exome

AF:

0.000308

Gnomad4 AMR exome

AF:

0.000279

Gnomad4 ASJ exome

AF:

0.0000777

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.00150

Gnomad4 OTH exome

AF:

0.00125

GnomAD4 genome

AF:

0.000610

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000900

Hom.:

Bravo

AF:

0.000695

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000560

AC:

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

Oct 07, 2022

The c.113C>A (p.A38E) 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 113, causing the alanine (A) at amino acid position 38 to be replaced by a glutamic acid (E). 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

Benign

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.0083

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.78

N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.98

N;N

REVEL

Benign

0.042

Sift

Benign

0.53

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.0040

B;B

Vest4

0.27

MVP

0.44

MPC

0.18

ClinPred

0.018

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.67

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

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