rs10999511

Positions:

• chr10-70752022-T-C

Variant summary

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

The NM_080722.4(ADAMTS14):​c.2597-73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,550,842 control chromosomes in the GnomAD database, including 54,921 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 0.24 (4706 hom., cov: 34)
  • Exomes 𝑓: 0.26 (50215 hom.)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673

Genes affected

ADAMTS14 (HGNC:14899): (ADAM metallopeptidase with thrombospondin type 1 motif 14) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) 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 enzyme. This enzyme cleaves amino-terminal propeptides from type I procollagen, a necessary step in the formation of collagen fibers. Mutations in this gene may be associated with osteoarthritis in human patients. [provided by RefSeq, May 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 (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.2597-73T>C		intron_variant		ENST00000373207.2	NP_542453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2	c.2597-73T>C		intron_variant		1	NM_080722.4	ENSP00000362303	P4
ADAMTS14	ENST00000373208.5	c.2606-73T>C		intron_variant		2		ENSP00000362304	A2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36189 AN: 152038 Hom.: 4701 Cov.: 34

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.259 AC: 362808 AN: 1398686 Hom.: 50215 AF XY: 0.262 AC XY: 180849 AN XY: 689448

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.586

Gnomad4 SAS exome AF: 0.355

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.258

GnomAD4 genome AF: 0.238 AC: 36213 AN: 152156 Hom.: 4706 Cov.: 34 AF XY: 0.241 AC XY: 17921 AN XY: 74394

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.236

Alfa AF: 0.239 Hom.: 728

Bravo AF: 0.231

Asia WGS AF: 0.457 AC: 1584 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	3.0
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10999511; hg19: chr10-72511778; COSMIC: COSV64602180;