21-28885293-G-C

Position:

chr21-28885293-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013240.6(N6AMT1):c.53C>G(p.Ala18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,591,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

N6AMT1
NM_013240.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0970

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077543944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
N6AMT1	NM_013240.6 linkuse as main transcript	c.53C>G	p.Ala18Gly	missense_variant	1/6	ENST00000303775.10	NP_037372.4	Q9Y5N5-1
N6AMT1	NM_182749.5 linkuse as main transcript	c.53C>G	p.Ala18Gly	missense_variant	1/5		NP_877426.4	Q9Y5N5-2
N6AMT1	NR_047510.3 linkuse as main transcript	n.75C>G		non_coding_transcript_exon_variant	1/7
N6AMT1	XR_007067787.1 linkuse as main transcript	n.75C>G		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.53C>G	p.Ala18Gly	missense_variant	1/6	1	NM_013240.6	ENSP00000303584.5	Q9Y5N5-1
N6AMT1	ENST00000351429.7 linkuse as main transcript	c.53C>G	p.Ala18Gly	missense_variant	1/5	1		ENSP00000286764.4	Q9Y5N5-2
N6AMT1	ENST00000460212.1 linkuse as main transcript	n.53C>G		non_coding_transcript_exon_variant	1/7	1		ENSP00000436490.1	Q9Y5N5-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152218

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000205

AC:

AN:

244210

Hom.:

AF XY:

0.00000754

AC XY:

AN XY:

132680

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000174

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.0000167

AC:

AN:

1439086

Hom.:

Cov.:

AF XY:

0.00000983

AC XY:

AN XY:

712392

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000157

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.13e-7

Gnomad4 OTH exome

AF:

0.000270

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Feb 05, 2024

The c.53C>G (p.A18G) alteration is located in exon 1 (coding exon 1) of the N6AMT1 gene. This alteration results from a C to G substitution at nucleotide position 53, causing the alanine (A) at amino acid position 18 to be replaced by a glycine (G). 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

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.039

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.85

.;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.078

T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.049

Sift

Benign

0.26

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.0

B;B

Vest4

0.28

MutPred

0.54

Gain of disorder (P = 0.0481);Gain of disorder (P = 0.0481);

MVP

0.14

MPC

0.15

ClinPred

0.028

GERP RS

-1.6

Varity_R

0.11

gMVP

0.60

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