NM_020682.4:c.2-97T>G

Variant names:

• chr10-102869708-T-G
• rs3740400
• NM_020682.4:c.2-97T>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.2-97T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,575,006 control chromosomes in the GnomAD database, including 109,722 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 0.39 (11043 hom., cov: 31)
  • Exomes 𝑓: 0.37 (98679 hom.)
• Consequence: AS3MT NM_020682.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 30 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]

ENSG00000296999 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020682.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AS3MT	NM_020682.4	MANE Select	c.2-97T>G		intron	N/A	NP_065733.2	Q9HBK9-1
	BORCS7-ASMT	NR_037644.1		n.407-97T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AS3MT	ENST00000369880.8	TSL:1 MANE Select	c.2-97T>G		intron	N/A	ENSP00000358896.3	Q9HBK9-1
	BORCS7-ASMT	ENST00000299353.6	TSL:5	n.*9-97T>G		intron	N/A	ENSP00000299353.5
	AS3MT	ENST00000942423.1		c.2-97T>G		intron	N/A	ENSP00000612482.1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 57110 AN: 147076 Hom.: 11029 Cov.: 31

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.412

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.371 AC: 530124 AN: 1427828 Hom.: 98679 Cov.: 36 AF XY: 0.374 AC XY: 265963 AN XY: 710582

African (AFR) AF: 0.374 AC: 12186 AN: 32546

American (AMR) AF: 0.402 AC: 17590 AN: 43726

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 10470 AN: 25076

East Asian (EAS) AF: 0.527 AC: 20121 AN: 38162

South Asian (SAS) AF: 0.447 AC: 38351 AN: 85842

European-Finnish (FIN) AF: 0.339 AC: 16279 AN: 48030

Middle Eastern (MID) AF: 0.439 AC: 2475 AN: 5632

European-Non Finnish (NFE) AF: 0.357 AC: 389786 AN: 1090374

Other (OTH) AF: 0.391 AC: 22866 AN: 58440

GnomAD4 genome AF: 0.388 AC: 57166 AN: 147178 Hom.: 11043 Cov.: 31 AF XY: 0.388 AC XY: 27850 AN XY: 71694

African (AFR) AF: 0.382 AC: 15177 AN: 39742

American (AMR) AF: 0.397 AC: 5848 AN: 14712

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1441 AN: 3450

East Asian (EAS) AF: 0.586 AC: 2892 AN: 4934

South Asian (SAS) AF: 0.458 AC: 2089 AN: 4558

European-Finnish (FIN) AF: 0.340 AC: 3305 AN: 9718

Middle Eastern (MID) AF: 0.419 AC: 119 AN: 284

European-Non Finnish (NFE) AF: 0.378 AC: 25295 AN: 66830

Other (OTH) AF: 0.397 AC: 819 AN: 2064

Alfa AF: 0.304 Hom.: 1410

Bravo AF: 0.382

Asia WGS AF: 0.441 AC: 1505 AN: 3424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.55
PhyloP100		-1.9
PromoterAI		0.018	Neutral

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: rs3740400; hg19: chr10-104629465; COSMIC: COSV54916132; COSMIC: COSV54916132;