rs61573157

Variant names:

• chr10-70760503-C-T
• rs61573157
• NM_080722.4:c.3322C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080722.4(ADAMTS14):​c.3322C>T​(p.Pro1108Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 1,613,844 control chromosomes in the GnomAD database, including 7,622 homozygotes. 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: 𝑓 0.076 (572 hom., cov: 33)
  • Exomes 𝑓: 0.095 (7050 hom.)
• Consequence: ADAMTS14 NM_080722.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 13 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 (MetaRNN=0.0017440319).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	NM_080722.4	MANE Select	c.3322C>T	p.Pro1108Ser	missense	Exon 22 of 22	NP_542453.2
	ADAMTS14	NM_139155.3		c.3331C>T	p.Pro1111Ser	missense	Exon 22 of 22	NP_631894.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	ENST00000373207.2	TSL:1 MANE Select	c.3322C>T	p.Pro1108Ser	missense	Exon 22 of 22	ENSP00000362303.1
	ADAMTS14	ENST00000373208.5	TSL:2	c.3331C>T	p.Pro1111Ser	missense	Exon 22 of 22	ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 11539 AN: 152130 Hom.: 571 Cov.: 33

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.0543

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.0980

Gnomad SAS AF: 0.0739

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0801

GnomAD2 exomes AF: 0.0857 AC: 21298 AN: 248402 AF XY: 0.0883

Gnomad AFR exome AF: 0.0164

Gnomad AMR exome AF: 0.0412

Gnomad ASJ exome AF: 0.0825

Gnomad EAS exome AF: 0.0941

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.0931

GnomAD4 exome AF: 0.0951 AC: 138940 AN: 1461596 Hom.: 7050 Cov.: 32 AF XY: 0.0949 AC XY: 69015 AN XY: 727072

African (AFR) AF: 0.0150 AC: 502 AN: 33480

American (AMR) AF: 0.0436 AC: 1948 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0806 AC: 2106 AN: 26118

East Asian (EAS) AF: 0.0798 AC: 3167 AN: 39698

South Asian (SAS) AF: 0.0776 AC: 6689 AN: 86226

European-Finnish (FIN) AF: 0.132 AC: 7012 AN: 53278

Middle Eastern (MID) AF: 0.100 AC: 578 AN: 5766

European-Non Finnish (NFE) AF: 0.100 AC: 111562 AN: 1111934

Other (OTH) AF: 0.0890 AC: 5376 AN: 60388

GnomAD4 genome AF: 0.0757 AC: 11523 AN: 152248 Hom.: 572 Cov.: 33 AF XY: 0.0761 AC XY: 5663 AN XY: 74432

African (AFR) AF: 0.0187 AC: 776 AN: 41562

American (AMR) AF: 0.0542 AC: 829 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 299 AN: 3468

East Asian (EAS) AF: 0.0974 AC: 504 AN: 5174

South Asian (SAS) AF: 0.0731 AC: 353 AN: 4828

European-Finnish (FIN) AF: 0.130 AC: 1374 AN: 10604

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7020 AN: 68000

Other (OTH) AF: 0.0792 AC: 167 AN: 2108

Alfa AF: 0.0877 Hom.: 279

Bravo AF: 0.0694

TwinsUK AF: 0.0998 AC: 370

ALSPAC AF: 0.104 AC: 399

ESP6500AA AF: 0.0245 AC: 108

ESP6500EA AF: 0.105 AC: 906

ExAC AF: 0.0871 AC: 10577

Asia WGS AF: 0.0720 AC: 251 AN: 3478

EpiCase AF: 0.0990

EpiControl AF: 0.0982

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.36
DANN	Benign	0.24
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L
PhyloP100		-0.092
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.013
Sift	Benign	0.87	T
Sift4G	Benign	0.87	T
Polyphen		0.0020	B
Vest4		0.022
MPC		0.17
ClinPred		0.00042	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.017
gMVP		0.18
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61573157; hg19: chr10-72520259; COSMIC: COSV64602584;