NM_020682.4:c.355A>G

Variant names:

• chr10-102873130-A-G
• rs767695284
• NM_020682.4:c.355A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020682.4(AS3MT):​c.355A>G​(p.Met119Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000138 in 1,451,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: AS3MT NM_020682.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2836285).

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.355A>G	p.Met119Val	missense	Exon 5 of 11	NP_065733.2	Q9HBK9-1
	BORCS7-ASMT	NR_037644.1		n.760A>G		non_coding_transcript_exon	Exon 9 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AS3MT	ENST00000369880.8	TSL:1 MANE Select	c.355A>G	p.Met119Val	missense	Exon 5 of 11	ENSP00000358896.3	Q9HBK9-1
	BORCS7-ASMT	ENST00000299353.6	TSL:5	n.*362A>G		non_coding_transcript_exon	Exon 9 of 15	ENSP00000299353.5
	BORCS7-ASMT	ENST00000299353.6	TSL:5	n.*362A>G		3_prime_UTR	Exon 9 of 15	ENSP00000299353.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000837 AC: 2 AN: 238966 AF XY: 0.0000154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000138 AC: 20 AN: 1451208 Hom.: 0 Cov.: 30 AF XY: 0.0000194 AC XY: 14 AN XY: 721610

African (AFR) AF: 0.000183 AC: 6 AN: 32828

American (AMR) AF: 0.00 AC: 0 AN: 41528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25726

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.0000361 AC: 3 AN: 83200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5730

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1109302

Other (OTH) AF: 0.000100 AC: 6 AN: 60000

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.081
Eigen_PC	Benign	0.073
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.8
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.067
Sift	Benign	0.11	T
Polyphen		0.061	B
Vest4		0.53
MutPred		0.45		Loss of ubiquitination at K121 (P = 0.0587)
MVP		0.31
MPC		0.68
ClinPred		0.65	D
GERP RS		4.5
Varity_R		0.21
gMVP		0.51

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: rs767695284; hg19: chr10-104632887;