10-102869708-T-C

Variant names:

• chr10-102869708-T-C
• rs3740400
• NM_020682.4:c.2-97T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020682.4(AS3MT):​c.2-97T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000317 in 1,575,260 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AS3MT NM_020682.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 30 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]

ENSG00000296999 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.2-97T>C		intron	N/A	NP_065733.2	Q9HBK9-1
	BORCS7-ASMT	NR_037644.1		n.407-97T>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.2-97T>C		intron	N/A	ENSP00000358896.3	Q9HBK9-1
	BORCS7-ASMT	ENST00000299353.6	TSL:5	n.*9-97T>C		intron	N/A	ENSP00000299353.5
	AS3MT	ENST00000942423.1		c.2-97T>C		intron	N/A	ENSP00000612482.1

Frequencies

GnomAD3 genomes AF: 0.0000204 AC: 3 AN: 147130 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000757

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1428130 Hom.: 0 Cov.: 36 AF XY: 0.00000141 AC XY: 1 AN XY: 710732

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000307 AC: 1 AN: 32556

American (AMR) AF: 0.00 AC: 0 AN: 43734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25084

East Asian (EAS) AF: 0.00 AC: 0 AN: 38164

South Asian (SAS) AF: 0.00 AC: 0 AN: 85848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1090582

Other (OTH) AF: 0.00 AC: 0 AN: 58452

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000204 AC: 3 AN: 147130 Hom.: 0 Cov.: 31 AF XY: 0.0000279 AC XY: 2 AN XY: 71612

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000757 AC: 3 AN: 39642

American (AMR) AF: 0.00 AC: 0 AN: 14702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 4946

South Asian (SAS) AF: 0.00 AC: 0 AN: 4582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66854

Other (OTH) AF: 0.00 AC: 0 AN: 2042

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0136242), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1410

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.67
PhyloP100		-1.9
PromoterAI		0.051	Neutral

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: rs3740400; hg19: chr10-104629465;