rs10823607

Variant names:

• chr10-70741007-T-G
• rs10823607
• NM_080722.4:c.1769T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-70741007-T-G
• chr10-70741007-T-A
• chr10-70741007-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080722.4(ADAMTS14):​c.1769T>G​(p.Leu590Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ADAMTS14 NM_080722.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.911
• Publications: 34 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1534302).

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.1769T>G	p.Leu590Arg	missense	Exon 12 of 22	NP_542453.2	Q8WXS8-1
	ADAMTS14	NM_139155.3		c.1778T>G	p.Leu593Arg	missense	Exon 12 of 22	NP_631894.2	Q8WXS8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	ENST00000373207.2	TSL:1 MANE Select	c.1769T>G	p.Leu590Arg	missense	Exon 12 of 22	ENSP00000362303.1	Q8WXS8-1
	ADAMTS14	ENST00000886732.1		c.1778T>G	p.Leu593Arg	missense	Exon 12 of 22	ENSP00000556791.1
	ADAMTS14	ENST00000373208.5	TSL:2	c.1778T>G	p.Leu593Arg	missense	Exon 12 of 22	ENSP00000362304.1	Q8WXS8-4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152102 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 68

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152102 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74316

African (AFR) AF: 0.00 AC: 0 AN: 41368

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	10
DANN	Benign	0.91
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.11	N
PhyloP100		0.91
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.047
Sift	Benign	0.54	T
Sift4G	Benign	0.36	T
Polyphen		0.089	B
Vest4		0.28
MutPred		0.62		Gain of disorder (P = 0.0442)
MVP		0.35
MPC		0.29
ClinPred		0.073	T
GERP RS		-2.5
Varity_R		0.11
gMVP		0.20
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10823607; hg19: chr10-72500763;