rs3740394

Variant names:

• chr10-102874717-A-G
• rs3740394
• NM_020682.4:c.528+56A>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.528+56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 1,292,182 control chromosomes in the GnomAD database, including 7,057 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 0.11 (898 hom., cov: 32)
  • Exomes 𝑓: 0.098 (6159 hom.)
• Consequence: AS3MT NM_020682.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AS3MT	NM_020682.4	c.528+56A>G		intron_variant	Intron 6 of 10	ENST00000369880.8	NP_065733.2
BORCS7-ASMT	NR_037644.1	n.933+56A>G		intron_variant	Intron 10 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AS3MT	ENST00000369880.8	c.528+56A>G		intron_variant	Intron 6 of 10	1	NM_020682.4	ENSP00000358896.3
BORCS7-ASMT	ENST00000299353.6	n.*535+56A>G		intron_variant	Intron 10 of 14	5		ENSP00000299353.5

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16280 AN: 152072 Hom.: 897 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0701

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0977 AC: 111360 AN: 1139992 Hom.: 6159 AF XY: 0.0969 AC XY: 55806 AN XY: 575934

Gnomad4 AFR exome AF: 0.124 AC: 3274 AN: 26326

Gnomad4 AMR exome AF: 0.0987 AC: 3692 AN: 37410

Gnomad4 ASJ exome AF: 0.117 AC: 2778 AN: 23796

Gnomad4 EAS exome AF: 0.0158 AC: 559 AN: 35298

Gnomad4 SAS exome AF: 0.0667 AC: 4977 AN: 74606

Gnomad4 FIN exome AF: 0.0667 AC: 3338 AN: 50022

Gnomad4 NFE exome AF: 0.103 AC: 86604 AN: 837752

Gnomad4 Remaining exome AF: 0.104 AC: 5188 AN: 49740

GnomAD4 genome AF: 0.107 AC: 16287 AN: 152190 Hom.: 898 Cov.: 32 AF XY: 0.105 AC XY: 7837 AN XY: 74420

Gnomad4 AFR AF: 0.125 AC: 0.12538 AN: 0.12538

Gnomad4 AMR AF: 0.122 AC: 0.122269 AN: 0.122269

Gnomad4 ASJ AF: 0.121 AC: 0.120749 AN: 0.120749

Gnomad4 EAS AF: 0.0162 AC: 0.0162037 AN: 0.0162037

Gnomad4 SAS AF: 0.0621 AC: 0.0621375 AN: 0.0621375

Gnomad4 FIN AF: 0.0701 AC: 0.0700547 AN: 0.0700547

Gnomad4 NFE AF: 0.107 AC: 0.107217 AN: 0.107217

Gnomad4 OTH AF: 0.107 AC: 0.106635 AN: 0.106635

Alfa AF: 0.111 Hom.: 171

Bravo AF: 0.113

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs3740394; hg19: chr10-104634474;