rs10785430

Positions:

• chr12-43425495-G-A
• chr12-43425495-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS20	NM_025003.5	c.4284+19C>T		intron_variant		ENST00000389420.8
ADAMTS20	XM_011538754.3	c.4287+19C>T		intron_variant
ADAMTS20	XM_017019979.2	c.3072+19C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS20	ENST00000389420.8	c.4284+19C>T		intron_variant		1	NM_025003.5	P1
ADAMTS20	ENST00000549670.5	c.1674+19C>T		intron_variant		2
ADAMTS20	ENST00000553158.5	c.4284+19C>T		intron_variant		5

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

GnomAD3 exomes AF: 0.560 AC: 96371 AN: 171950 Hom.: 27874 AF XY: 0.563 AC XY: 52489 AN XY: 93178

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 SAS exome AF: 0.664

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

Gnomad4 AFR exome AF: 0.659

Gnomad4 AMR exome AF: 0.453

Gnomad4 ASJ exome AF: 0.636

Gnomad4 EAS exome AF: 0.828

Gnomad4 SAS exome AF: 0.663

Gnomad4 FIN exome AF: 0.545

Gnomad4 NFE exome AF: 0.507

Gnomad4 OTH exome AF: 0.567

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

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.854

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.577

Alfa AF: 0.527 Hom.: 29078

Bravo AF: 0.573

Asia WGS AF: 0.776 AC: 2699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.40

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: rs10785430; hg19: chr12-43819298;