rs10506226

Positions:

• chr12-43375425-A-C
• chr12-43375425-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_025003.5(ADAMTS20):​c.5400T>G​(p.Thr1800Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,612,308 control chromosomes in the GnomAD database, including 35,466 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 (5240 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30226 hom.)
• Consequence: ADAMTS20 NM_025003.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-0.884 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS20	NM_025003.5	c.5400T>G	p.Thr1800Thr	synonymous_variant	36/39	ENST00000389420.8	NP_079279.3
ADAMTS20	XM_011538754.3	c.5403T>G	p.Thr1801Thr	synonymous_variant	36/39		XP_011537056.1
ADAMTS20	XM_017019979.2	c.4188T>G	p.Thr1396Thr	synonymous_variant	29/32		XP_016875468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS20	ENST00000389420.8	c.5400T>G	p.Thr1800Thr	synonymous_variant	36/39	1	NM_025003.5	ENSP00000374071.3

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37584 AN: 151924 Hom.: 5239 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.198 AC: 49731 AN: 250880 Hom.: 5653 AF XY: 0.198 AC XY: 26909 AN XY: 135606

Gnomad AFR exome AF: 0.379

Gnomad AMR exome AF: 0.112

Gnomad ASJ exome AF: 0.267

Gnomad EAS exome AF: 0.109

Gnomad SAS exome AF: 0.179

Gnomad FIN exome AF: 0.246

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.198 AC: 289349 AN: 1460266 Hom.: 30226 Cov.: 32 AF XY: 0.198 AC XY: 143747 AN XY: 726496

Gnomad4 AFR exome AF: 0.380

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.247 AC: 37604 AN: 152042 Hom.: 5240 Cov.: 32 AF XY: 0.246 AC XY: 18255 AN XY: 74344

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.223

Alfa AF: 0.205 Hom.: 4507

Bravo AF: 0.245

Asia WGS AF: 0.153 AC: 531 AN: 3476

EpiCase AF: 0.215

EpiControl AF: 0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10506226; hg19: chr12-43769228; COSMIC: COSV67132149;