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GeneBe

21-28885327-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013240.6(N6AMT1):c.19G>A(p.Ala7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000468 in 1,581,958 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000039 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

N6AMT1
NM_013240.6 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.32
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.022351563).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
N6AMT1NM_013240.6 linkuse as main transcriptc.19G>A p.Ala7Thr missense_variant 1/6 ENST00000303775.10
N6AMT1NM_182749.5 linkuse as main transcriptc.19G>A p.Ala7Thr missense_variant 1/5
N6AMT1NR_047510.3 linkuse as main transcriptn.41G>A non_coding_transcript_exon_variant 1/7
N6AMT1XR_007067787.1 linkuse as main transcriptn.41G>A non_coding_transcript_exon_variant 1/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
N6AMT1ENST00000303775.10 linkuse as main transcriptc.19G>A p.Ala7Thr missense_variant 1/61 NM_013240.6 P1Q9Y5N5-1
N6AMT1ENST00000351429.7 linkuse as main transcriptc.19G>A p.Ala7Thr missense_variant 1/51 Q9Y5N5-2
N6AMT1ENST00000460212.1 linkuse as main transcriptc.19G>A p.Ala7Thr missense_variant, NMD_transcript_variant 1/71 Q9Y5N5-1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152214
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00116
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
GnomAD3 exomes
AF:
0.0000913
AC:
22
AN:
240984
Hom.:
0
AF XY:
0.0000840
AC XY:
11
AN XY:
130990
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00131
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000476
AC:
68
AN:
1429626
Hom.:
0
Cov.:
38
AF XY:
0.0000439
AC XY:
31
AN XY:
706242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00172
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000184
Gnomad4 OTH exome
AF:
0.0000170
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152332
Hom.:
0
Cov.:
34
AF XY:
0.0000403
AC XY:
3
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000982
ExAC
AF:
0.0000989
AC:
12

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 submitterclinical testingAmbry GeneticsMay 17, 2023The c.19G>A (p.A7T) 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 19, causing the alanine (A) at amino acid position 7 to be replaced by a threonine (T). 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
0.14
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.60
Cadd
Benign
19
Dann
Uncertain
0.98
DEOGEN2
Benign
0.021
T;.
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.56
FATHMM_MKL
Uncertain
0.89
D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.022
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.35
N;N
REVEL
Benign
0.080
Sift
Benign
0.039
D;D
Sift4G
Uncertain
0.044
D;D
Polyphen
0.084
B;B
Vest4
0.20
MVP
0.24
MPC
0.15
ClinPred
0.11
T
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.12
gMVP
0.79

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.

Other links and lift over

dbSNP: rs199505140; hg19: chr21-30257649; API