dbSNP rs3740392: AS3MT:c.610+63T>C (chr10-102877098-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_020682.4(AS3MT):c.610+63T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.25 (AC=370,792) in the gnomAD database across 1,481,194 control chromosomes, including 47,616 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.313. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 4724 hom., cov: 32)

Exomes 𝑓: 0.25 ( 42892 hom. )

Consequence

AS3MT
NM_020682.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31

Publications

32 publications found

Variant links:

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]

AS3MT links:

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 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_020682.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.3131 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_020682.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AS3MT	NM_020682.4	MANE Select	c.610+63T>C		intron	N/A	NP_065733.2	Q9HBK9-1
	BORCS7-ASMT	NR_037644.1		n.1015+63T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AS3MT	ENST00000369880.8	TSL:1 MANE Select	c.610+63T>C	intron	N/A	ENSP00000358896.3	Q9HBK9-1
BORCS7-ASMT	ENST00000299353.6	TSL:5	n.*617+63T>C	intron	N/A	ENSP00000299353.5	Q96B45
AS3MT	ENST00000942423.1		c.595+63T>C	intron	N/A	ENSP00000612482.1	A0ACI8U690

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37439

AN:

152114

Hom.:

4722

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.255

GnomAD4 exome

AF:

0.251

AC:

333342

AN:

1328962

Hom.:

42892

AF XY:

0.252

AC XY:

167995

AN XY:

667908

show subpopulations

African (AFR)

AF:

0.221

AC:

6796

AN:

30726

American (AMR)

AF:

0.187

AC:

8297

AN:

44404

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

7801

AN:

25186

East Asian (EAS)

AF:

0.240

AC:

9348

AN:

39030

South Asian (SAS)

AF:

0.241

AC:

20084

AN:

83194

European-Finnish (FIN)

AF:

0.223

AC:

11498

AN:

51668

Middle Eastern (MID)

AF:

0.326

AC:

1793

AN:

5506

European-Non Finnish (NFE)

AF:

0.255

AC:

253319

AN:

993406

Other (OTH)

AF:

0.258

AC:

14406

AN:

55842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

11894

23788

35681

47575

59469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8048

16096

24144

32192

40240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.246

AC:

37450

AN:

152232

Hom.:

4724

Cov.:

AF XY:

0.244

AC XY:

18184

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.223

AC:

9278

AN:

41546

American (AMR)

AF:

0.223

AC:

3407

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

1140

AN:

3472

East Asian (EAS)

AF:

0.282

AC:

1463

AN:

5182

South Asian (SAS)

AF:

0.250

AC:

1206

AN:

4830

European-Finnish (FIN)

AF:

0.216

AC:

2287

AN:

10598

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17890

AN:

67990

Other (OTH)

AF:

0.254

AC:

536

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1487

2974

4461

5948

7435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.255

Hom.:

3717

Bravo

AF:

0.245

Asia WGS

AF:

0.242

AC:

840

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.186

AC:

22780

AN:

122684

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.309

AC:

2766

AN:

8960

Hom.:

426

ABraOM SABE-WGS-1171

AF:

0.254

AC:

594

AN:

2342

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.3

(source)

DANN

Benign

0.72

PhyloP100

1.3

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over