chr10-102873130-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020682.4(AS3MT):ā€‹c.355A>Gā€‹(p.Met119Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000138 in 1,451,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.000014 ( 0 hom. )

Consequence

AS3MT
NM_020682.4 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2836285).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AS3MTNM_020682.4 linkuse as main transcriptc.355A>G p.Met119Val missense_variant 5/11 ENST00000369880.8
BORCS7-ASMTNR_037644.1 linkuse as main transcriptn.760A>G non_coding_transcript_exon_variant 9/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AS3MTENST00000369880.8 linkuse as main transcriptc.355A>G p.Met119Val missense_variant 5/111 NM_020682.4 P1Q9HBK9-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000837
AC:
2
AN:
238966
Hom.:
0
AF XY:
0.0000154
AC XY:
2
AN XY:
129566
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000181
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000138
AC:
20
AN:
1451208
Hom.:
0
Cov.:
30
AF XY:
0.0000194
AC XY:
14
AN XY:
721610
show subpopulations
Gnomad4 AFR exome
AF:
0.000183
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000361
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000361
Gnomad4 OTH exome
AF:
0.000100
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000756
ExAC
AF:
0.0000248
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 27, 2022The c.355A>G (p.M119V) alteration is located in exon 5 (coding exon 5) of the AS3MT gene. This alteration results from a A to G substitution at nucleotide position 355, causing the methionine (M) at amino acid position 119 to be replaced by a valine (V). 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
0.078
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
21
DANN
Benign
0.94
DEOGEN2
Benign
0.030
T;T
Eigen
Benign
-0.081
Eigen_PC
Benign
0.073
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.28
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
.;L
PrimateAI
Benign
0.35
T
PROVEAN
Uncertain
-2.5
.;N
REVEL
Benign
0.067
Sift
Benign
0.11
.;T
Polyphen
0.061
.;B
Vest4
0.53
MutPred
0.45
Loss of ubiquitination at K121 (P = 0.0587);Loss of ubiquitination at K121 (P = 0.0587);
MVP
0.31
MPC
0.68
ClinPred
0.65
D
GERP RS
4.5
Varity_R
0.21
gMVP
0.51

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

LitVar

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

Other links and lift over

dbSNP: rs767695284; hg19: chr10-104632887; API