Genetic Variant AS3MT:c.-114G>C (chr10-102869479-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020682.4(AS3MT):c.-114G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0546 in 1,346,796 control chromosomes in the GnomAD database, including 5,243 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 0.14 ( 1973 hom., cov: 32)

Exomes 𝑓: 0.043 ( 3270 hom. )

Consequence

AS3MT
NM_020682.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

Publications

16 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:

ENSG00000296999 (HGNC:):

ENSG00000296999 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AS3MT	NM_020682.4 link	c.-114G>C		5_prime_UTR_variant	Exon 1 of 11	ENST00000369880.8	NP_065733.2	Q9HBK9-1
BORCS7-ASMT	NR_037644.1 link	n.407-326G>C		intron_variant	Intron 5 of 14

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AS3MT	ENST00000369880.8 link	c.-114G>C	5_prime_UTR_variant	Exon 1 of 11	1	NM_020682.4	ENSP00000358896.3	Q9HBK9-1
BORCS7-ASMT	ENST00000299353.6 link	n.*9-326G>C	intron_variant	Intron 5 of 14	5		ENSP00000299353.5	A0A0B4J1R7
ENSG00000296999	ENST00000744161.1 link	n.87+1343C>G	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

21898

AN:

151208

Hom.:

1966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.0849

Gnomad SAS

AF:

0.0833

Gnomad FIN

AF:

0.0726

Gnomad MID

AF:

0.192

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.136

GnomAD4 exome

AF:

0.0432

AC:

51616

AN:

1195476

Hom.:

3270

Cov.:

AF XY:

0.0462

AC XY:

27463

AN XY:

594730

show subpopulations

African (AFR)

AF:

0.137

AC:

3118

AN:

22832

American (AMR)

AF:

0.0671

AC:

2171

AN:

32370

Ashkenazi Jewish (ASJ)

AF:

0.0769

AC:

1706

AN:

22198

East Asian (EAS)

AF:

0.0839

AC:

2950

AN:

35180

South Asian (SAS)

AF:

0.0559

AC:

4122

AN:

73800

European-Finnish (FIN)

AF:

0.0687

AC:

2302

AN:

33498

Middle Eastern (MID)

AF:

0.119

AC:

399

AN:

3344

European-Non Finnish (NFE)

AF:

0.0342

AC:

31506

AN:

921176

Other (OTH)

AF:

0.0654

AC:

3342

AN:

51078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

2365

4729

7094

9458

11823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

392

588

784

980

<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:

0.145

AC:

21927

AN:

151320

Hom.:

1973

Cov.:

AF XY:

0.143

AC XY:

10544

AN XY:

73972

show subpopulations

African (AFR)

AF:

0.245

AC:

10034

AN:

40936

American (AMR)

AF:

0.137

AC:

2091

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

448

AN:

3462

East Asian (EAS)

AF:

0.0845

AC:

434

AN:

5134

South Asian (SAS)

AF:

0.0842

AC:

405

AN:

4812

European-Finnish (FIN)

AF:

0.0726

AC:

770

AN:

10606

Middle Eastern (MID)

AF:

0.203

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.108

AC:

7305

AN:

67814

Other (OTH)

AF:

0.135

AC:

284

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

907

1814

2720

3627

4534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<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:

0.133

Hom.:

207

Bravo

AF:

0.158

Asia WGS

AF:

0.0670

AC:

225

AN:

3360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.6

(source)

DANN

Benign

0.54

PhyloP100

1.2

PromoterAI

-0.022

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over