rs7085854

Variant names:

• chr10-102890494-T-C
• rs7085854
• NM_020682.4:c.886-50T>C

Variant summary

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

The NM_020682.4(AS3MT):​c.886-50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,491,920 control chromosomes in the GnomAD database, including 33,502 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 0.21 (3451 hom., cov: 31)
  • Exomes 𝑓: 0.21 (30051 hom.)
• Consequence: AS3MT NM_020682.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 15 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.219 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.886-50T>C		intron	N/A	NP_065733.2	Q9HBK9-1
	BORCS7-ASMT	NR_037644.1		n.1291-50T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AS3MT	ENST00000369880.8	TSL:1 MANE Select	c.886-50T>C		intron	N/A	ENSP00000358896.3	Q9HBK9-1
	BORCS7-ASMT	ENST00000299353.6	TSL:5	n.*893-50T>C		intron	N/A	ENSP00000299353.5
	AS3MT	ENST00000942423.1		c.871-50T>C		intron	N/A	ENSP00000612482.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31777 AN: 151932 Hom.: 3453 Cov.: 31

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.208

GnomAD2 exomes AF: 0.198 AC: 34549 AN: 174644 AF XY: 0.199

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.232

Gnomad EAS exome AF: 0.200

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.209 AC: 279643 AN: 1339870 Hom.: 30051 Cov.: 20 AF XY: 0.208 AC XY: 137546 AN XY: 662142

African (AFR) AF: 0.218 AC: 6333 AN: 29068

American (AMR) AF: 0.122 AC: 3607 AN: 29568

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 4741 AN: 20596

East Asian (EAS) AF: 0.143 AC: 5383 AN: 37536

South Asian (SAS) AF: 0.171 AC: 11829 AN: 69372

European-Finnish (FIN) AF: 0.219 AC: 10937 AN: 49952

Middle Eastern (MID) AF: 0.163 AC: 859 AN: 5286

European-Non Finnish (NFE) AF: 0.215 AC: 224379 AN: 1043008

Other (OTH) AF: 0.209 AC: 11575 AN: 55484

GnomAD4 genome AF: 0.209 AC: 31795 AN: 152050 Hom.: 3451 Cov.: 31 AF XY: 0.206 AC XY: 15302 AN XY: 74316

African (AFR) AF: 0.213 AC: 8819 AN: 41464

American (AMR) AF: 0.143 AC: 2185 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 845 AN: 3472

East Asian (EAS) AF: 0.197 AC: 1019 AN: 5176

South Asian (SAS) AF: 0.174 AC: 840 AN: 4822

European-Finnish (FIN) AF: 0.219 AC: 2317 AN: 10572

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15068 AN: 67958

Other (OTH) AF: 0.210 AC: 443 AN: 2112

Alfa AF: 0.210 Hom.: 809

Bravo AF: 0.202

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		0.29

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: rs7085854; hg19: chr10-104650251; COSMIC: COSV54918590; COSMIC: COSV54918590;