4-72288783-G-C

Variant names:

• chr4-72288783-G-C
• NM_014243.3:c.3017C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014243.3(ADAMTS3):​c.3017C>G​(p.Ser1006Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,558 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ADAMTS3 NM_014243.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.95

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS3	NM_014243.3	c.3017C>G	p.Ser1006Trp	missense_variant	Exon 21 of 22	ENST00000286657.10	NP_055058.2
ADAMTS3	XM_011532421.2	c.2960C>G	p.Ser987Trp	missense_variant	Exon 21 of 22		XP_011530723.1
ADAMTS3	XM_011532422.4	c.2933C>G	p.Ser978Trp	missense_variant	Exon 21 of 22		XP_011530724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS3	ENST00000286657.10	c.3017C>G	p.Ser1006Trp	missense_variant	Exon 21 of 22	1	NM_014243.3	ENSP00000286657.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461558 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727068

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Pathogenic	3.6	H;H
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.4	D;.
REVEL	Uncertain	0.39
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.99	D;D
Vest4		0.48
MutPred		0.61		Loss of disorder (P = 2e-04);Loss of disorder (P = 2e-04);
MVP		0.87
MPC		0.61
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.26
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-73154500;