10-102877098-T-C

Position:

• chr10-102877098-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020682.4(AS3MT):​c.610+63T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,481,194 control chromosomes in the GnomAD database, including 47,616 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (4724 hom., cov: 32)
  • Exomes 𝑓: 0.25 (42892 hom.)
• Consequence: AS3MT NM_020682.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AS3MT	NM_020682.4	c.610+63T>C		intron_variant		ENST00000369880.8
BORCS7-ASMT	NR_037644.1	n.1015+63T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AS3MT	ENST00000369880.8	c.610+63T>C		intron_variant		1	NM_020682.4	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37439 AN: 152114 Hom.: 4722 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.251 AC: 333342 AN: 1328962 Hom.: 42892 AF XY: 0.252 AC XY: 167995 AN XY: 667908

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.258

GnomAD4 genome AF: 0.246 AC: 37450 AN: 152232 Hom.: 4724 Cov.: 32 AF XY: 0.244 AC XY: 18184 AN XY: 74428

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.254

Alfa AF: 0.254 Hom.: 2282

Bravo AF: 0.245

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.3
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs3740392; hg19: chr10-104636855; COSMIC: COSV54919782;