10-102890629-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020682.4(AS3MT):ā€‹c.971T>Cā€‹(p.Ile324Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000068 ( 0 hom. )

Consequence

AS3MT
NM_020682.4 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.348
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03834775).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AS3MTNM_020682.4 linkuse as main transcriptc.971T>C p.Ile324Thr missense_variant 10/11 ENST00000369880.8 NP_065733.2
BORCS7-ASMTNR_037644.1 linkuse as main transcriptn.1376T>C non_coding_transcript_exon_variant 14/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AS3MTENST00000369880.8 linkuse as main transcriptc.971T>C p.Ile324Thr missense_variant 10/111 NM_020682.4 ENSP00000358896 P1Q9HBK9-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152118
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000459
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
248968
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135104
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000582
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:
0.00
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461358
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726980
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152118
Hom.:
0
Cov.:
31
AF XY:
0.0000807
AC XY:
6
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000459
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.000106

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 GeneticsNov 22, 2023The c.971T>C (p.I324T) alteration is located in exon 10 (coding exon 10) of the AS3MT gene. This alteration results from a T to C substitution at nucleotide position 971, causing the isoleucine (I) at amino acid position 324 to be replaced by a threonine (T). 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
0.049
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.84
DANN
Benign
0.76
DEOGEN2
Benign
0.0087
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.61
T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.038
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
.;L
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.37
.;N
REVEL
Benign
0.030
Sift
Benign
0.46
.;T
Polyphen
0.0
.;B
Vest4
0.090
MutPred
0.40
Gain of phosphorylation at I324 (P = 0.0277);Gain of phosphorylation at I324 (P = 0.0277);
MVP
0.24
MPC
0.42
ClinPred
0.025
T
GERP RS
-1.4
Varity_R
0.067
gMVP
0.32

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: rs928210555; hg19: chr10-104650386; API