Variant 21-28885341-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000303775.10(N6AMT1):c.5C>T(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000255 in 1,568,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

N6AMT1
ENST00000303775.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.01

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	Protein
N6AMT1	NM_013240.6 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/6	ENST00000303775.10	NP_037372.4
N6AMT1	NM_182749.5 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/5		NP_877426.4
N6AMT1	NR_047510.3 linkuse as main transcript	n.27C>T		non_coding_transcript_exon_variant	1/7
N6AMT1	XR_007067787.1 linkuse as main transcript	n.27C>T		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.5C>T	p.Ala2Val	missense_variant	1/6	1	NM_013240.6	ENSP00000303584	P1	Q9Y5N5-1
N6AMT1	ENST00000351429.7 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/5	1		ENSP00000286764		Q9Y5N5-2
N6AMT1	ENST00000460212.1 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant, NMD_transcript_variant	1/7	1		ENSP00000436490		Q9Y5N5-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152176

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:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000850

AC:

AN:

235378

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

128342

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000340

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000930

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1415754

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

698166

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000480

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000596

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000204

Gnomad4 OTH exome

AF:

0.0000516

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.00000824

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

Jun 21, 2021

The c.5C>T (p.A2V) alteration is located in exon 1 (coding exon 1) of the N6AMT1 gene. This alteration results from a C to T substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by a valine (V). 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

0.19

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.25

.;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.96

N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.57

N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0070

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.31

MutPred

0.23

Loss of disorder (P = 0.1247);Loss of disorder (P = 0.1247);

MVP

0.39

MPC

0.22

ClinPred

0.74

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.051

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.40

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.40

Position offset: 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