chr10-102878462-A-C

Variant names:

• chr10-102878462-A-C
• NM_020682.4:c.694A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020682.4(AS3MT):​c.694A>C​(p.Thr232Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 1.39
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30135024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AS3MT	NM_020682.4	c.694A>C	p.Thr232Pro	missense_variant	Exon 8 of 11	ENST00000369880.8	NP_065733.2
BORCS7-ASMT	NR_037644.1	n.1099A>C		non_coding_transcript_exon_variant	Exon 12 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AS3MT	ENST00000369880.8	c.694A>C	p.Thr232Pro	missense_variant	Exon 8 of 11	1	NM_020682.4	ENSP00000358896.3
BORCS7-ASMT	ENST00000299353.6	n.*701A>C		non_coding_transcript_exon_variant	Exon 12 of 15	5		ENSP00000299353.5
BORCS7-ASMT	ENST00000299353.6	n.*701A>C		3_prime_UTR_variant	Exon 12 of 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

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.694A>C (p.T232P) alteration is located in exon 8 (coding exon 8) of the AS3MT gene. This alteration results from a A to C substitution at nucleotide position 694, causing the threonine (T) at amino acid position 232 to be replaced by a proline (P). 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	Uncertain	0.49
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T;T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.4	.;M
PhyloP100		1.4
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.9	.;D
REVEL	Benign	0.20
Sift	Uncertain	0.013	.;D
Polyphen		0.93	.;P
Vest4		0.37
MutPred		0.61		Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);
MVP		0.52
MPC		1.2
ClinPred		0.96	D
GERP RS		1.6
Varity_R		0.65
gMVP		0.86

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

Other links and lift over

hg19: chr10-104638219;