10-102878966-T-C

Variant names:

• chr10-102878966-T-C
• rs11191439
• NM_020682.4:c.860T>C

Variant summary

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

The NM_020682.4(AS3MT):​c.860T>C​(p.Met287Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 1,612,308 control chromosomes in the GnomAD database, including 8,407 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.10 (852 hom., cov: 31)
  • Exomes 𝑓: 0.097 (7555 hom.)
• Consequence: AS3MT NM_020682.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001987338).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AS3MT	NM_020682.4	c.860T>C	p.Met287Thr	missense_variant	Exon 9 of 11	ENST00000369880.8	NP_065733.2
BORCS7-ASMT	NR_037644.1	n.1265T>C		non_coding_transcript_exon_variant	Exon 13 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AS3MT	ENST00000369880.8	c.860T>C	p.Met287Thr	missense_variant	Exon 9 of 11	1	NM_020682.4	ENSP00000358896.3
BORCS7-ASMT	ENST00000299353.6	n.*867T>C		non_coding_transcript_exon_variant	Exon 13 of 15	5		ENSP00000299353.5
BORCS7-ASMT	ENST00000299353.6	n.*867T>C		3_prime_UTR_variant	Exon 13 of 15	5		ENSP00000299353.5

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15842 AN: 152090 Hom.: 851 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.0689

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.108

GnomAD3 exomes AF: 0.0919 AC: 22826 AN: 248258 Hom.: 1180 AF XY: 0.0915 AC XY: 12322 AN XY: 134678

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.0932

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.0141

Gnomad SAS exome AF: 0.0690

Gnomad FIN exome AF: 0.0649

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.0975 AC: 142324 AN: 1460098 Hom.: 7555 Cov.: 31 AF XY: 0.0968 AC XY: 70333 AN XY: 726326

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.0964

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.0160

Gnomad4 SAS exome AF: 0.0700

Gnomad4 FIN exome AF: 0.0671

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.104 AC: 15850 AN: 152210 Hom.: 852 Cov.: 31 AF XY: 0.103 AC XY: 7643 AN XY: 74432

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.0694

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.105

Alfa AF: 0.104 Hom.: 1957

Bravo AF: 0.110

TwinsUK AF: 0.107 AC: 395

ALSPAC AF: 0.108 AC: 417

ESP6500AA AF: 0.115 AC: 434

ESP6500EA AF: 0.103 AC: 843

ExAC AF: 0.0934 AC: 11285

Asia WGS AF: 0.0560 AC: 195 AN: 3478

EpiCase AF: 0.111

EpiControl AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.21
DEOGEN2	Benign	0.0061	T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.83
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.61	T;T
MetaRNN	Benign	0.0020	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.080	.;N
REVEL	Benign	0.049
Sift	Benign	0.57	.;T
Polyphen		0.0	.;B
Vest4		0.018
MPC		0.39
ClinPred		0.00023	T
GERP RS		2.9
Varity_R		0.019
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

Publications

LitVar

Other links and lift over

dbSNP: rs11191439; hg19: chr10-104638723; COSMIC: COSV54916951;