rs788919

Positions:

• chr4-72488177-T-C

Variant summary

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

The ENST00000286657.10(ADAMTS3):​c.504+60301A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,762 control chromosomes in the GnomAD database, including 5,539 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 0.27 (5539 hom., cov: 31)
• Consequence: ADAMTS3 ENST00000286657.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176

Genes affected

ADAMTS3 (HGNC:219): (ADAM metallopeptidase with thrombospondin type 1 motif 3) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease, a member of the procollagen aminopropeptidase subfamily of proteins, may play a role in the processing of type II fibrillar collagen in articular cartilage. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS3	NM_014243.3	c.504+60301A>G		intron_variant		ENST00000286657.10	NP_055058.2
ADAMTS3	XM_011532421.2	c.447+60301A>G		intron_variant			XP_011530723.1
ADAMTS3	XM_011532422.4	c.420+60301A>G		intron_variant			XP_011530724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS3	ENST00000286657.10	c.504+60301A>G		intron_variant		1	NM_014243.3	ENSP00000286657	P1
ADAMTS3	ENST00000505193.1	n.462-45961A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40608 AN: 151642 Hom.: 5532 Cov.: 31

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.268 AC: 40646 AN: 151762 Hom.: 5539 Cov.: 31 AF XY: 0.268 AC XY: 19853 AN XY: 74174

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.273

Alfa AF: 0.269 Hom.: 5775

Bravo AF: 0.274

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.5
DANN	Benign	0.68

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: rs788919; hg19: chr4-73353894;