Genetic Variant NM_020682.4:c.311C>T (chr10-102872588-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020682.4(AS3MT):c.311C>T(p.Thr104Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

AS3MT
NM_020682.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.52

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 made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AS3MT	NM_020682.4 link	c.311C>T	p.Thr104Ile	missense_variant	Exon 4 of 11	ENST00000369880.8	NP_065733.2	Q9HBK9-1
BORCS7-ASMT	NR_037644.1 link	n.716C>T		non_coding_transcript_exon_variant	Exon 8 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AS3MT	ENST00000369880.8 link	c.311C>T	p.Thr104Ile	missense_variant	Exon 4 of 11	1	NM_020682.4	ENSP00000358896.3	Q9HBK9-1
BORCS7-ASMT	ENST00000299353.6 link	n.*318C>T		non_coding_transcript_exon_variant	Exon 8 of 15	5		ENSP00000299353.5	A0A0B4J1R7
BORCS7-ASMT	ENST00000299353.6 link	n.*318C>T		3_prime_UTR_variant	Exon 8 of 15	5		ENSP00000299353.5	A0A0B4J1R7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000166

AC:

AN:

240368

Hom.:

AF XY:

0.0000229

AC XY:

AN XY:

130746

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000228

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454852

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723726

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.031

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-0.64

MutationAssessor

Pathogenic

3.1

.;M

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-5.7

.;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

.;D

Polyphen

1.0

.;D

Vest4

0.94

MutPred

0.55

Loss of disorder (P = 0.0485);Loss of disorder (P = 0.0485);

MVP

0.70

MPC

1.1

ClinPred

0.99

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.69

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over