NM_020682.4:c.1020+1045A>G

Variant names:

• chr10-102891723-A-G
• rs11191446
• NM_020682.4:c.1020+1045A>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.1020+1045A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,104 control chromosomes in the GnomAD database, including 901 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 (901 hom., cov: 31)
• Consequence: AS3MT NM_020682.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.117 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AS3MT	NM_020682.4	MANE Select	c.1020+1045A>G		intron	N/A	NP_065733.2
	BORCS7-ASMT	NR_037644.1		n.1425+1045A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AS3MT	ENST00000369880.8	TSL:1 MANE Select	c.1020+1045A>G		intron	N/A	ENSP00000358896.3
	BORCS7-ASMT	ENST00000299353.6	TSL:5	n.*1027+1045A>G		intron	N/A	ENSP00000299353.5

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16422 AN: 151986 Hom.: 900 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0870

Gnomad SAS AF: 0.0898

Gnomad FIN AF: 0.0728

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.108 AC: 16435 AN: 152104 Hom.: 901 Cov.: 31 AF XY: 0.107 AC XY: 7990 AN XY: 74358

African (AFR) AF: 0.119 AC: 4954 AN: 41510

American (AMR) AF: 0.121 AC: 1842 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 425 AN: 3464

East Asian (EAS) AF: 0.0870 AC: 450 AN: 5170

South Asian (SAS) AF: 0.0907 AC: 436 AN: 4808

European-Finnish (FIN) AF: 0.0728 AC: 772 AN: 10598

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7175 AN: 68006

Other (OTH) AF: 0.109 AC: 229 AN: 2106

Alfa AF: 0.110 Hom.: 128

Bravo AF: 0.113

Asia WGS AF: 0.0980 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.66
PhyloP100		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11191446; hg19: chr10-104651480;