rs275380

chr12-43536193-A-Cchr12-43536193-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025003.5(ADAMTS20):c.454-3998T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 152,114 control chromosomes in the GnomAD database, including 66,494 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 0.93 (66494 hom., cov: 31)
• Consequence: ADAMTS20 NM_025003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS20	NM_025003.5	c.454-3998T>G		intron_variant		ENST00000389420.8
ADAMTS20	XM_011538754.3	c.454-3998T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS20	ENST00000389420.8	c.454-3998T>G		intron_variant		1	NM_025003.5	P1
ADAMTS20	ENST00000553158.5	c.454-3998T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.933 AC: 141740 AN: 151998 Hom.: 66461 Cov.: 31

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.941

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

GnomAD4 genome AF: 0.932 AC: 141829 AN: 152114 Hom.: 66494 Cov.: 31 AF XY: 0.935 AC XY: 69525 AN XY: 74372

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.963

Gnomad4 ASJ AF: 0.960

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.979

Gnomad4 FIN AF: 0.988

Gnomad4 NFE AF: 0.973

Gnomad4 OTH AF: 0.942

Alfa AF: 0.967 Hom.: 148851

Bravo AF: 0.925

Asia WGS AF: 0.976 AC: 3392 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.5
Dann	Benign	0.53

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: rs275380; hg19: chr12-43929996;