10-102878664-A-C

Variant names:

• chr10-102878664-A-C
• rs3740391
• NM_020682.4:c.742+154A>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.742+154A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,132 control chromosomes in the GnomAD database, including 1,266 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 0.13 (1266 hom., cov: 31)
• Consequence: AS3MT NM_020682.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 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.742+154A>C		intron	N/A	NP_065733.2	Q9HBK9-1
	BORCS7-ASMT	NR_037644.1		n.1147+154A>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.742+154A>C		intron	N/A	ENSP00000358896.3	Q9HBK9-1
	BORCS7-ASMT	ENST00000299353.6	TSL:5	n.*749+154A>C		intron	N/A	ENSP00000299353.5
	AS3MT	ENST00000942423.1		c.727+154A>C		intron	N/A	ENSP00000612482.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19011 AN: 152014 Hom.: 1265 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.125 AC: 19018 AN: 152132 Hom.: 1266 Cov.: 31 AF XY: 0.122 AC XY: 9061 AN XY: 74364

African (AFR) AF: 0.101 AC: 4185 AN: 41508

American (AMR) AF: 0.122 AC: 1856 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3472

East Asian (EAS) AF: 0.148 AC: 764 AN: 5178

South Asian (SAS) AF: 0.151 AC: 727 AN: 4820

European-Finnish (FIN) AF: 0.0652 AC: 691 AN: 10604

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9467 AN: 67982

Other (OTH) AF: 0.159 AC: 336 AN: 2112

Alfa AF: 0.119 Hom.: 165

Bravo AF: 0.130

Asia WGS AF: 0.143 AC: 497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.41
DANN	Benign	0.36
PhyloP100		-0.70

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: rs3740391; hg19: chr10-104638421; COSMIC: COSV54919255;