12-43400628-T-C

Variant names:

• chr12-43400628-T-C
• rs10506227
• NM_025003.5:c.4285-1395A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025003.5(ADAMTS20):​c.4285-1395A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 151,856 control chromosomes in the GnomAD database, including 1,293 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 0.088 (1293 hom., cov: 32)
• Consequence: ADAMTS20 NM_025003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 3 publications found

Genes affected

ADAMTS20 (HGNC:17178): (ADAM metallopeptidase with thrombospondin type 1 motif 20) The protein encoded by this gene is a member of the ADAMTS family of zinc-dependent proteases. The encoded protein has a signal peptide that is cleaved to release the mature peptide, which is secreted and found in the extracellular matrix. This protein may be involved in tissue remodeling. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025003.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS20	NM_025003.5	MANE Select	c.4285-1395A>G		intron	N/A	NP_079279.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS20	ENST00000389420.8	TSL:1 MANE Select	c.4285-1395A>G		intron	N/A	ENSP00000374071.3

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13322 AN: 151738 Hom.: 1288 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0664

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0509

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0742

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0879 AC: 13353 AN: 151856 Hom.: 1293 Cov.: 32 AF XY: 0.0853 AC XY: 6333 AN XY: 74230

African (AFR) AF: 0.244 AC: 10125 AN: 41420

American (AMR) AF: 0.0383 AC: 583 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.0664 AC: 230 AN: 3462

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5164

South Asian (SAS) AF: 0.0511 AC: 246 AN: 4814

European-Finnish (FIN) AF: 0.0211 AC: 224 AN: 10604

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0257 AC: 1746 AN: 67842

Other (OTH) AF: 0.0734 AC: 155 AN: 2112

Alfa AF: 0.0444 Hom.: 1657

Bravo AF: 0.0958

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.67
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs10506227; hg19: chr12-43794431;