10-102890620-T-C

Position:

• chr10-102890620-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020682.4(AS3MT):​c.962T>C​(p.Ile321Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: AS3MT NM_020682.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.78

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]

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]

ACMG classification

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=0.4135251).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AS3MT	NM_020682.4	c.962T>C	p.Ile321Thr	missense_variant	10/11	ENST00000369880.8	NP_065733.2
BORCS7-ASMT	NR_037644.1	n.1367T>C		non_coding_transcript_exon_variant	14/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AS3MT	ENST00000369880.8	c.962T>C	p.Ile321Thr	missense_variant	10/11	1	NM_020682.4	ENSP00000358896.3
BORCS7-ASMT	ENST00000299353.6	n.*969T>C		non_coding_transcript_exon_variant	14/15	5		ENSP00000299353.5
BORCS7-ASMT	ENST00000299353.6	n.*969T>C		3_prime_UTR_variant	14/15	5		ENSP00000299353.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.962T>C (p.I321T) 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 962, causing the isoleucine (I) at amino acid position 321 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	0.29
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	0.053
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.4	.;N
REVEL	Benign	0.19
Sift	Uncertain	0.0090	.;D
Polyphen		0.038	.;B
Vest4		0.53
MutPred		0.62		Loss of stability (P = 0.0059);Loss of stability (P = 0.0059);
MVP		0.65
MPC		0.69
ClinPred		0.85	D
GERP RS		5.3
Varity_R		0.15
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-104650377;