chr10-102870074-G-T

Variant names:

• chr10-102870074-G-T
• rs17880345
• NM_020682.4:c.43-10G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020682.4(AS3MT):​c.43-10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00639 in 1,613,416 control chromosomes in the GnomAD database, including 493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (263 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (230 hom.)
• Consequence: AS3MT NM_020682.4 intron
• Scores: Splicing: ADA: 0.00006680
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.784
• Publications: 2 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]

ENSG00000296999 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 10-102870074-G-T is Benign according to our data. Variant chr10-102870074-G-T is described in ClinVar as [Benign]. Clinvar id is 768385.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AS3MT	NM_020682.4	c.43-10G>T		intron_variant	Intron 2 of 10	ENST00000369880.8	NP_065733.2
BORCS7-ASMT	NR_037644.1	n.448-10G>T		intron_variant	Intron 6 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AS3MT	ENST00000369880.8	c.43-10G>T		intron_variant	Intron 2 of 10	1	NM_020682.4	ENSP00000358896.3
BORCS7-ASMT	ENST00000299353.6	n.*50-10G>T		intron_variant	Intron 6 of 14	5		ENSP00000299353.5
ENSG00000296999	ENST00000744161.1	n.87+748C>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4740 AN: 152134 Hom.: 263 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0220

GnomAD2 exomes AF: 0.00866 AC: 2149 AN: 248184 AF XY: 0.00671

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.00496

Gnomad ASJ exome AF: 0.0112

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000736

Gnomad OTH exome AF: 0.00448

GnomAD4 exome AF: 0.00380 AC: 5559 AN: 1461164 Hom.: 230 Cov.: 33 AF XY: 0.00335 AC XY: 2435 AN XY: 726898

African (AFR) AF: 0.117 AC: 3913 AN: 33464

American (AMR) AF: 0.00593 AC: 265 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00984 AC: 257 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52876

Middle Eastern (MID) AF: 0.00815 AC: 47 AN: 5768

European-Non Finnish (NFE) AF: 0.000487 AC: 541 AN: 1111900

Other (OTH) AF: 0.00843 AC: 509 AN: 60384

GnomAD4 genome AF: 0.0312 AC: 4750 AN: 152252 Hom.: 263 Cov.: 32 AF XY: 0.0299 AC XY: 2229 AN XY: 74460

African (AFR) AF: 0.108 AC: 4471 AN: 41526

American (AMR) AF: 0.0112 AC: 172 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00721 AC: 25 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68030

Other (OTH) AF: 0.0218 AC: 46 AN: 2114

Alfa AF: 0.0207 Hom.: 46

Bravo AF: 0.0357

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.2
DANN	Benign	0.88
PhyloP100		-0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000067
SpliceAI score (max)		0.040		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

dbSNP: rs17880345; hg19: chr10-104629831;