Variant chr21-28883046-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_013240.6(N6AMT1):c.160T>G(p.Ser54Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,784 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

N6AMT1
NM_013240.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.77

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27223986).

BP6

Variant 21-28883046-A-C is Benign according to our data. Variant chr21-28883046-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2318179.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
N6AMT1	NM_013240.6 linkuse as main transcript	c.160T>G	p.Ser54Ala	missense_variant	2/6	ENST00000303775.10
N6AMT1	NM_182749.5 linkuse as main transcript	c.160T>G	p.Ser54Ala	missense_variant	2/5
N6AMT1	NR_047510.3 linkuse as main transcript	n.182T>G		non_coding_transcript_exon_variant	2/7
N6AMT1	XR_007067787.1 linkuse as main transcript	n.182T>G		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
N6AMT1	ENST00000303775.10 linkuse as main transcript	c.160T>G	p.Ser54Ala	missense_variant	2/6	1	NM_013240.6	P1	Q9Y5N5-1
N6AMT1	ENST00000351429.7 linkuse as main transcript	c.160T>G	p.Ser54Ala	missense_variant	2/5	1			Q9Y5N5-2
N6AMT1	ENST00000460212.1 linkuse as main transcript	c.160T>G	p.Ser54Ala	missense_variant, NMD_transcript_variant	2/7	1			Q9Y5N5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

247942

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134202

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:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1452784

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722688

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:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.072

T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.65

.;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.056

Sift

Benign

0.16

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.023

B;B

Vest4

0.21

MutPred

0.50

Loss of glycosylation at S54 (P = 0.0046);Loss of glycosylation at S54 (P = 0.0046);

MVP

0.19

MPC

0.13

ClinPred

0.054

GERP RS

1.6

Varity_R

0.30

gMVP

0.73

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