rs10999511

Variant names:

• chr10-70752022-T-C
• rs10999511
• NM_080722.4:c.2597-73T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080722.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	NM_080722.4	MANE Select	c.2597-73T>C		intron	N/A	NP_542453.2
	ADAMTS14	NM_139155.3		c.2606-73T>C		intron	N/A	NP_631894.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	ENST00000373207.2	TSL:1 MANE Select	c.2597-73T>C		intron	N/A	ENSP00000362303.1
	ADAMTS14	ENST00000886732.1		c.2639-73T>C		intron	N/A	ENSP00000556791.1
	ADAMTS14	ENST00000373208.5	TSL:2	c.2606-73T>C		intron	N/A	ENSP00000362304.1

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

African (AFR) AF: 0.160 AC: 5129 AN: 32000

American (AMR) AF: 0.228 AC: 8508 AN: 37302

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 4223 AN: 21818

East Asian (EAS) AF: 0.586 AC: 22895 AN: 39088

South Asian (SAS) AF: 0.355 AC: 26741 AN: 75414

European-Finnish (FIN) AF: 0.274 AC: 13403 AN: 48902

Middle Eastern (MID) AF: 0.197 AC: 1015 AN: 5162

European-Non Finnish (NFE) AF: 0.246 AC: 266016 AN: 1081376

Other (OTH) AF: 0.258 AC: 14878 AN: 57624

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

African (AFR) AF: 0.172 AC: 7159 AN: 41546

American (AMR) AF: 0.221 AC: 3374 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 713 AN: 3468

East Asian (EAS) AF: 0.560 AC: 2889 AN: 5158

South Asian (SAS) AF: 0.362 AC: 1748 AN: 4826

European-Finnish (FIN) AF: 0.267 AC: 2834 AN: 10602

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16714 AN: 67948

Other (OTH) AF: 0.236 AC: 499 AN: 2110

Alfa AF: 0.238 Hom.: 743

Bravo AF: 0.231

Asia WGS AF: 0.457 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.63
PhyloP100		-0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10999511; hg19: chr10-72511778; COSMIC: COSV64602180;