Variant 21-28885302-C-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.44G>A(p.Gly15Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,436,420 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

N6AMT1
NM_013240.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.54

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:

N6AMT1 (HGNC:):

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	UniProt
N6AMT1	NM_013240.6 linkuse as main transcript	c.44G>A	p.Gly15Asp	missense_variant	1/6	ENST00000303775.10	NP_037372.4	Q9Y5N5-1
N6AMT1	NM_182749.5 linkuse as main transcript	c.44G>A	p.Gly15Asp	missense_variant	1/5		NP_877426.4	Q9Y5N5-2
N6AMT1	NR_047510.3 linkuse as main transcript	n.66G>A		non_coding_transcript_exon_variant	1/7
N6AMT1	XR_007067787.1 linkuse as main transcript	n.66G>A		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
N6AMT1	ENST00000303775.10 linkuse as main transcript	c.44G>A	p.Gly15Asp	missense_variant	1/6	1	NM_013240.6	ENSP00000303584.5	Q9Y5N5-1
N6AMT1	ENST00000351429.7 linkuse as main transcript	c.44G>A	p.Gly15Asp	missense_variant	1/5	1		ENSP00000286764.4	Q9Y5N5-2
N6AMT1	ENST00000460212.1 linkuse as main transcript	n.44G>A		non_coding_transcript_exon_variant	1/7	1		ENSP00000436490.1	Q9Y5N5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

243702

Hom.:

AF XY:

0.00000755

AC XY:

AN XY:

132378

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1436420

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710492

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:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Aug 28, 2024

The c.44G>A (p.G15D) alteration is located in exon 1 (coding exon 1) of the N6AMT1 gene. This alteration results from a G to A substitution at nucleotide position 44, causing the glycine (G) at amino acid position 15 to be replaced by an aspartic acid (D). 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

0.52

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.68

.;T

M_CAP

Benign

0.0074

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.22

Sift

Benign

0.13

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.44

B;D

Vest4

0.72

MutPred

0.51

Gain of catalytic residue at G15 (P = 0.0245);Gain of catalytic residue at G15 (P = 0.0245);

MVP

0.37

MPC

0.21

ClinPred

0.92

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.84

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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