12-43513403-G-A

Variant names:

• chr12-43513403-G-A
• rs1510521
• NM_025003.5:c.614-10998C>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.614-10998C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,030 control chromosomes in the GnomAD database, including 36,945 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 0.69 (36945 hom., cov: 32)
• Consequence: ADAMTS20 NM_025003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 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.614-10998C>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.614-10998C>T		intron	N/A	ENSP00000374071.3
	ADAMTS20	ENST00000553158.5	TSL:5	c.614-10998C>T		intron	N/A	ENSP00000448341.1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105429 AN: 151912 Hom.: 36916 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.694 AC: 105514 AN: 152030 Hom.: 36945 Cov.: 32 AF XY: 0.700 AC XY: 52014 AN XY: 74310

African (AFR) AF: 0.713 AC: 29543 AN: 41462

American (AMR) AF: 0.731 AC: 11174 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2639 AN: 3472

East Asian (EAS) AF: 0.990 AC: 5131 AN: 5182

South Asian (SAS) AF: 0.804 AC: 3881 AN: 4828

European-Finnish (FIN) AF: 0.655 AC: 6899 AN: 10540

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 44014 AN: 67942

Other (OTH) AF: 0.710 AC: 1500 AN: 2112

Alfa AF: 0.654 Hom.: 16989

Bravo AF: 0.700

Asia WGS AF: 0.889 AC: 3090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.65
PhyloP100		0.53
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: rs1510521; hg19: chr12-43907206;