rs3740390

Positions:

• chr10-102878723-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020682.4(AS3MT):​c.743-126C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 1,362,820 control chromosomes in the GnomAD database, including 8,055 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 0.096 (900 hom., cov: 31)
  • Exomes 𝑓: 0.097 (7155 hom.)
• Consequence: AS3MT NM_020682.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.954

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]

BORCS7-ASMT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AS3MT	NM_020682.4	c.743-126C>T		intron_variant		ENST00000369880.8	NP_065733.2
BORCS7-ASMT	NR_037644.1	n.1148-126C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AS3MT	ENST00000369880.8	c.743-126C>T		intron_variant		1	NM_020682.4	ENSP00000358896.3
BORCS7-ASMT	ENST00000299353.6	n.*750-126C>T		intron_variant		5		ENSP00000299353.5

Frequencies

GnomAD3 genomes AF: 0.0961 AC: 14609 AN: 152026 Hom.: 895 Cov.: 31

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0967 AC: 117098 AN: 1210676 Hom.: 7155 AF XY: 0.0992 AC XY: 59589 AN XY: 600460

Gnomad4 AFR exome AF: 0.0544

Gnomad4 AMR exome AF: 0.195

Gnomad4 ASJ exome AF: 0.0787

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.0798

Gnomad4 NFE exome AF: 0.0825

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.0962 AC: 14635 AN: 152144 Hom.: 900 Cov.: 31 AF XY: 0.0978 AC XY: 7274 AN XY: 74378

Gnomad4 AFR AF: 0.0621

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.0755

Gnomad4 NFE AF: 0.0925

Gnomad4 OTH AF: 0.105

Alfa AF: 0.101 Hom.: 171

Bravo AF: 0.0999

Asia WGS AF: 0.201 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	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

Publications

LitVar

Other links and lift over

dbSNP: rs3740390; hg19: chr10-104638480;