10-102872497-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020682.4(AS3MT):c.220A>G(p.Ile74Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: AS3MT NM_020682.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.703

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AS3MT	NM_020682.4	c.220A>G	p.Ile74Val	missense_variant	4/11	ENST00000369880.8
BORCS7-ASMT	NR_037644.1	n.625A>G		non_coding_transcript_exon_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AS3MT	ENST00000369880.8	c.220A>G	p.Ile74Val	missense_variant	4/11	1	NM_020682.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461838 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

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

Sep 29, 2022

The c.220A>G (p.I74V) alteration is located in exon 4 (coding exon 4) of the AS3MT gene. This alteration results from a A to G substitution at nucleotide position 220, causing the isoleucine (I) at amino acid position 74 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	0.086
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	11
Dann	Benign	0.82
DEOGEN2	Benign	0.048	T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.39	T
Polyphen		0.0030	.;B
Vest4		0.16
MutPred		0.62		Gain of catalytic residue at I74 (P = 0.0403);Gain of catalytic residue at I74 (P = 0.0403);
MVP		0.32
MPC		0.29
ClinPred		0.17	T
GERP RS		1.7
Varity_R		0.026
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.41		Position offset: -49

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: chr10-104632254;