chr10-70753879-C-G

Position:

• chr10-70753879-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080722.4(ADAMTS14):​c.2809C>G​(p.Leu937Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L937M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ADAMTS14 NM_080722.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.06

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3579327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.2809C>G	p.Leu937Val	missense_variant	19/22	ENST00000373207.2	NP_542453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2	c.2809C>G	p.Leu937Val	missense_variant	19/22	1	NM_080722.4	ENSP00000362303.1
ADAMTS14	ENST00000373208.5	c.2818C>G	p.Leu940Val	missense_variant	19/22	2		ENSP00000362304.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0096	.;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.88	.;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.47	N;N
REVEL	Benign	0.096
Sift	Benign	0.15	T;T
Sift4G	Uncertain	0.013	D;D
Polyphen		0.66	.;P
Vest4		0.24
MutPred		0.26		.;Gain of MoRF binding (P = 0.0796);
MVP		0.63
MPC		0.48
ClinPred		0.88	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.14

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

LitVar

Other links and lift over

dbSNP: rs12774070; hg19: chr10-72513635;