Genetic Variant AS3MT:p.Val167Ala (chr10-102874633-T-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020682.4(AS3MT):c.500T>C(p.Val167Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AS3MT
NM_020682.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.13

Publications

0 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: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.855

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AS3MT	NM_020682.4 link	c.500T>C	p.Val167Ala	missense_variant	Exon 6 of 11	ENST00000369880.8	NP_065733.2	Q9HBK9-1
BORCS7-ASMT	NR_037644.1 link	n.905T>C		non_coding_transcript_exon_variant	Exon 10 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AS3MT	ENST00000369880.8 link	c.500T>C	p.Val167Ala	missense_variant	Exon 6 of 11	1	NM_020682.4	ENSP00000358896.3	Q9HBK9-1
BORCS7-ASMT	ENST00000299353.6 link	n.*507T>C		non_coding_transcript_exon_variant	Exon 10 of 15	5		ENSP00000299353.5	A0A0B4J1R7
BORCS7-ASMT	ENST00000299353.6 link	n.*507T>C		3_prime_UTR_variant	Exon 10 of 15	5		ENSP00000299353.5	A0A0B4J1R7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458148

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33324

American (AMR)

AF:

0.00

AC:

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39562

South Asian (SAS)

AF:

0.00

AC:

AN:

85560

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1109780

Other (OTH)

AF:

0.00

AC:

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 04, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.500T>C (p.V167A) alteration is located in exon 6 (coding exon 6) of the AS3MT gene. This alteration results from a T to C substitution at nucleotide position 500, causing the valine (V) at amino acid position 167 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.0088

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.026

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.6

.;L

PhyloP100

7.1

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.9

.;D

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

.;D

Polyphen

1.0

.;D

Vest4

0.70

MutPred

0.59

Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);

MVP

0.47

MPC

1.2

ClinPred

0.99

GERP RS

4.7

Varity_R

0.76

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over