chr4-72283167-C-A

Variant names:

• chr4-72283167-C-A
• NM_014243.3:c.3587G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014243.3(ADAMTS3):​c.3587G>T​(p.Arg1196Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ADAMTS3 NM_014243.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039823055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS3	NM_014243.3	c.3587G>T	p.Arg1196Leu	missense_variant	Exon 22 of 22	ENST00000286657.10	NP_055058.2
ADAMTS3	XM_011532421.2	c.3530G>T	p.Arg1177Leu	missense_variant	Exon 22 of 22		XP_011530723.1
ADAMTS3	XM_011532422.4	c.3503G>T	p.Arg1168Leu	missense_variant	Exon 22 of 22		XP_011530724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS3	ENST00000286657.10	c.3587G>T	p.Arg1196Leu	missense_variant	Exon 22 of 22	1	NM_014243.3	ENSP00000286657.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459798 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.15
DANN	Benign	0.78
DEOGEN2	Benign	0.020	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.39	N;.
REVEL	Benign	0.064
Sift	Benign	0.63	T;.
Sift4G	Benign	0.69	T;T
Polyphen		0.0080	B;B
Vest4		0.13
MutPred		0.37		Gain of glycosylation at S1200 (P = 0.0065);Gain of glycosylation at S1200 (P = 0.0065);
MVP		0.36
MPC		0.16
ClinPred		0.070	T
GERP RS		-4.9
Varity_R		0.050
gMVP		0.18

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: chr4-73148884;