NM_020682.4:c.459-335A>G

Variant names:

• chr10-102874257-A-G
• rs17881367
• NM_020682.4:c.459-335A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020682.4(AS3MT):​c.459-335A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00503 in 130,790 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0050 (19 hom., cov: 31)
• Consequence: AS3MT NM_020682.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 1 publications found

Genes affected

AS3MT (HGNC:17452): (arsenite methyltransferase) AS3MT catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (AdoMet) to trivalent arsenical and may play a role in arsenic metabolism (Lin et al., 2002 [PubMed 11790780]).[supplied by OMIM, Mar 2008]

BORCS7-ASMT (HGNC:49183): (BORCS7-ASMT readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring C10orf32 (chromosome 10 open reading frame 32) and AS3MT (arsenic, +3 oxidation state, methyltransferase) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AS3MT	NM_020682.4	c.459-335A>G		intron_variant	Intron 5 of 10	ENST00000369880.8	NP_065733.2
BORCS7-ASMT	NR_037644.1	n.864-335A>G		intron_variant	Intron 9 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AS3MT	ENST00000369880.8	c.459-335A>G		intron_variant	Intron 5 of 10	1	NM_020682.4	ENSP00000358896.3
BORCS7-ASMT	ENST00000299353.6	n.*466-335A>G		intron_variant	Intron 9 of 14	5		ENSP00000299353.5

Frequencies

GnomAD3 genomes AF: 0.00500 AC: 654 AN: 130752 Hom.: 19 Cov.: 31

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00154

Gnomad ASJ AF: 0.00267

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.0248

Gnomad FIN AF: 0.00494

Gnomad MID AF: 0.00394

Gnomad NFE AF: 0.000880

Gnomad OTH AF: 0.00456

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00503 AC: 658 AN: 130790 Hom.: 19 Cov.: 31 AF XY: 0.00609 AC XY: 388 AN XY: 63674

African (AFR) AF: 0.00158 AC: 56 AN: 35366

American (AMR) AF: 0.00154 AC: 20 AN: 12992

Ashkenazi Jewish (ASJ) AF: 0.00267 AC: 8 AN: 3000

East Asian (EAS) AF: 0.0728 AC: 361 AN: 4958

South Asian (SAS) AF: 0.0254 AC: 109 AN: 4296

European-Finnish (FIN) AF: 0.00494 AC: 41 AN: 8304

Middle Eastern (MID) AF: 0.00427 AC: 1 AN: 234

European-Non Finnish (NFE) AF: 0.000881 AC: 52 AN: 59048

Other (OTH) AF: 0.00564 AC: 10 AN: 1774

Alfa AF: 0.00361 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.97
DANN	Benign	0.10
PhyloP100		-0.37

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

Other links and lift over

dbSNP: rs17881367; hg19: chr10-104634014;