rs10748835

Variant names:

• chr10-102900499-G-A
• rs10748835
• NM_020682.4:c.1021-94G>A

Variant summary

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

The NM_020682.4(AS3MT):​c.1021-94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 864,272 control chromosomes in the GnomAD database, including 74,789 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 0.41 (12865 hom., cov: 32)
  • Exomes 𝑓: 0.41 (61924 hom.)
• Consequence: AS3MT NM_020682.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 53 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]

ENSG00000286575 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AS3MT	NM_020682.4	c.1021-94G>A		intron_variant	Intron 10 of 10	ENST00000369880.8	NP_065733.2
LOC107984265	NR_160733.1	n.180C>T		non_coding_transcript_exon_variant	Exon 2 of 3
BORCS7-ASMT	NR_037644.1	n.1426-94G>A		intron_variant	Intron 14 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AS3MT	ENST00000369880.8	c.1021-94G>A		intron_variant	Intron 10 of 10	1	NM_020682.4	ENSP00000358896.3
BORCS7-ASMT	ENST00000299353.6	n.*1028-94G>A		intron_variant	Intron 14 of 14	5		ENSP00000299353.5

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61975 AN: 151940 Hom.: 12853 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.415 AC: 295456 AN: 712214 Hom.: 61924 AF XY: 0.417 AC XY: 155667 AN XY: 373710

African (AFR) AF: 0.380 AC: 7025 AN: 18478

American (AMR) AF: 0.418 AC: 14424 AN: 34524

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 7990 AN: 18850

East Asian (EAS) AF: 0.497 AC: 17104 AN: 34416

South Asian (SAS) AF: 0.457 AC: 28487 AN: 62356

European-Finnish (FIN) AF: 0.372 AC: 18408 AN: 49460

Middle Eastern (MID) AF: 0.447 AC: 1472 AN: 3290

European-Non Finnish (NFE) AF: 0.408 AC: 185931 AN: 455842

Other (OTH) AF: 0.418 AC: 14615 AN: 34998

GnomAD4 genome AF: 0.408 AC: 62031 AN: 152058 Hom.: 12865 Cov.: 32 AF XY: 0.406 AC XY: 30178 AN XY: 74322

African (AFR) AF: 0.378 AC: 15658 AN: 41462

American (AMR) AF: 0.402 AC: 6127 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1516 AN: 3468

East Asian (EAS) AF: 0.559 AC: 2890 AN: 5172

South Asian (SAS) AF: 0.449 AC: 2164 AN: 4820

European-Finnish (FIN) AF: 0.368 AC: 3897 AN: 10588

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28438 AN: 67974

Other (OTH) AF: 0.422 AC: 892 AN: 2114

Alfa AF: 0.421 Hom.: 2828

Bravo AF: 0.409

Asia WGS AF: 0.467 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.38
PhyloP100		-0.31

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: rs10748835; hg19: chr10-104660256;