Genetic Variant NM_020682.4:c.743-126C>T (chr10-102878723-C-T) – 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.743-126C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 1,362,820 control chromosomes in the GnomAD database, including 8,055 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 0.096 ( 900 hom., cov: 31)

Exomes 𝑓: 0.097 ( 7155 hom. )

Consequence

AS3MT
NM_020682.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.954

Publications

58 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

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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AS3MT	NM_020682.4 link	c.743-126C>T		intron_variant	Intron 8 of 10	ENST00000369880.8	NP_065733.2	Q9HBK9-1
BORCS7-ASMT	NR_037644.1 link	n.1148-126C>T		intron_variant	Intron 12 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AS3MT	ENST00000369880.8 link	c.743-126C>T		intron_variant	Intron 8 of 10	1	NM_020682.4	ENSP00000358896.3		Q9HBK9-1
BORCS7-ASMT	ENST00000299353.6 link	n.*750-126C>T		intron_variant	Intron 12 of 14	5		ENSP00000299353.5		A0A0B4J1R7

Frequencies

GnomAD3 genomes

AF:

0.0961

AC:

14609

AN:

152026

Hom.:

895

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0619

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.0706

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.0755

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0925

Gnomad OTH

AF:

0.102

GnomAD4 exome

AF:

0.0967

AC:

117098

AN:

1210676

Hom.:

7155

AF XY:

0.0992

AC XY:

59589

AN XY:

600460

show subpopulations

African (AFR)

AF:

0.0544

AC:

1426

AN:

26218

American (AMR)

AF:

0.195

AC:

5188

AN:

26648

Ashkenazi Jewish (ASJ)

AF:

0.0787

AC:

1507

AN:

19142

East Asian (EAS)

AF:

0.266

AC:

9717

AN:

36586

South Asian (SAS)

AF:

0.197

AC:

12633

AN:

64002

European-Finnish (FIN)

AF:

0.0798

AC:

3752

AN:

47040

Middle Eastern (MID)

AF:

0.0910

AC:

458

AN:

5032

European-Non Finnish (NFE)

AF:

0.0825

AC:

77139

AN:

934746

Other (OTH)

AF:

0.103

AC:

5278

AN:

51262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5033

10067

15100

20134

25167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2910

5820

8730

11640

14550

<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:

0.0962

AC:

14635

AN:

152144

Hom.:

900

Cov.:

AF XY:

0.0978

AC XY:

7274

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0621

AC:

2579

AN:

41506

American (AMR)

AF:

0.140

AC:

2144

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0706

AC:

245

AN:

3468

East Asian (EAS)

AF:

0.278

AC:

1439

AN:

5170

South Asian (SAS)

AF:

0.183

AC:

884

AN:

4830

European-Finnish (FIN)

AF:

0.0755

AC:

798

AN:

10570

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0925

AC:

6288

AN:

67996

Other (OTH)

AF:

0.105

AC:

221

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

649

1297

1946

2594

3243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.100

Hom.:

173

Bravo

AF:

0.0999

Asia WGS

AF:

0.201

AC:

695

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.0

(source)

DANN

Benign

0.70

PhyloP100

-0.95

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