chr12-43375425-A-C

Variant names:

• chr12-43375425-A-C
• rs10506226
• NM_025003.5:c.5400T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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]

ENSG00000305349 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.5400T>G	p.Thr1800Thr	synonymous	Exon 36 of 39	NP_079279.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS20	ENST00000389420.8	TSL:1 MANE Select	c.5400T>G	p.Thr1800Thr	synonymous	Exon 36 of 39	ENSP00000374071.3
	ENSG00000305349	ENST00000810541.1		n.133-3577A>C		intron	N/A

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

GnomAD2 exomes AF: 0.198 AC: 49731 AN: 250880 AF XY: 0.198

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 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

African (AFR) AF: 0.380 AC: 12708 AN: 33416

American (AMR) AF: 0.116 AC: 5170 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 7123 AN: 26104

East Asian (EAS) AF: 0.122 AC: 4831 AN: 39658

South Asian (SAS) AF: 0.182 AC: 15723 AN: 86180

European-Finnish (FIN) AF: 0.245 AC: 13071 AN: 53356

Middle Eastern (MID) AF: 0.253 AC: 1459 AN: 5760

European-Non Finnish (NFE) AF: 0.195 AC: 216793 AN: 1110776

Other (OTH) AF: 0.207 AC: 12471 AN: 60324

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

African (AFR) AF: 0.372 AC: 15422 AN: 41432

American (AMR) AF: 0.171 AC: 2611 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 955 AN: 3468

East Asian (EAS) AF: 0.107 AC: 555 AN: 5172

South Asian (SAS) AF: 0.172 AC: 828 AN: 4820

European-Finnish (FIN) AF: 0.241 AC: 2554 AN: 10580

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13971 AN: 67976

Other (OTH) AF: 0.223 AC: 470 AN: 2110

Alfa AF: 0.211 Hom.: 5864

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.44
PhyloP100		-0.88
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10506226; hg19: chr12-43769228; COSMIC: COSV67132149;