12-43425495-G-A

Variant names:

• chr12-43425495-G-A
• rs10785430
• NM_025003.5:c.4284+19C>T

Variant summary

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

The NM_025003.5(ADAMTS20):​c.4284+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,434,480 control chromosomes in the GnomAD database, including 210,283 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 0.57 (25505 hom., cov: 32)
  • Exomes 𝑓: 0.53 (184778 hom.)
• Consequence: ADAMTS20 NM_025003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.833 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.4284+19C>T		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.4284+19C>T		intron	N/A	ENSP00000374071.3
	ADAMTS20	ENST00000935091.1		c.4179+19C>T		intron	N/A	ENSP00000605150.1
	ADAMTS20	ENST00000553158.5	TSL:5	c.4284+19C>T		intron	N/A	ENSP00000448341.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87174 AN: 151884 Hom.: 25482 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.575

GnomAD2 exomes AF: 0.560 AC: 96371 AN: 171950 AF XY: 0.563

Gnomad AFR exome AF: 0.643

Gnomad AMR exome AF: 0.444

Gnomad ASJ exome AF: 0.630

Gnomad EAS exome AF: 0.858

Gnomad FIN exome AF: 0.541

Gnomad NFE exome AF: 0.511

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.531 AC: 680848 AN: 1282478 Hom.: 184778 Cov.: 30 AF XY: 0.534 AC XY: 334040 AN XY: 626022

African (AFR) AF: 0.659 AC: 18485 AN: 28068

American (AMR) AF: 0.453 AC: 12633 AN: 27882

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 12793 AN: 20102

East Asian (EAS) AF: 0.828 AC: 27794 AN: 33550

South Asian (SAS) AF: 0.663 AC: 37268 AN: 56224

European-Finnish (FIN) AF: 0.545 AC: 26155 AN: 47960

Middle Eastern (MID) AF: 0.623 AC: 3157 AN: 5070

European-Non Finnish (NFE) AF: 0.507 AC: 513119 AN: 1011704

Other (OTH) AF: 0.567 AC: 29444 AN: 51918

GnomAD4 genome AF: 0.574 AC: 87241 AN: 152002 Hom.: 25505 Cov.: 32 AF XY: 0.579 AC XY: 43017 AN XY: 74292

African (AFR) AF: 0.649 AC: 26895 AN: 41450

American (AMR) AF: 0.518 AC: 7910 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2237 AN: 3472

East Asian (EAS) AF: 0.854 AC: 4418 AN: 5176

South Asian (SAS) AF: 0.680 AC: 3275 AN: 4814

European-Finnish (FIN) AF: 0.547 AC: 5766 AN: 10536

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34914 AN: 67954

Other (OTH) AF: 0.577 AC: 1218 AN: 2112

Alfa AF: 0.531 Hom.: 37330

Bravo AF: 0.573

Asia WGS AF: 0.776 AC: 2699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		-0.17
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: rs10785430; hg19: chr12-43819298;