rs764571352

Variant names:

• chr10-70674723-C-G
• NM_080722.4:c.250C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-70674723-C-G
• chr10-70674723-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080722.4(ADAMTS14):​c.250C>G​(p.Arg84Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,140 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R84W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ADAMTS14 NM_080722.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.250C>G	p.Arg84Gly	missense_variant	Exon 2 of 22	ENST00000373207.2	NP_542453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2	c.250C>G	p.Arg84Gly	missense_variant	Exon 2 of 22	1	NM_080722.4	ENSP00000362303.1
ADAMTS14	ENST00000373208.5	c.250C>G	p.Arg84Gly	missense_variant	Exon 2 of 22	2		ENSP00000362304.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461140 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726844

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.052
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.47
Sift	Benign	0.036	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.96	.;D
Vest4		0.61
MutPred		0.59		Loss of MoRF binding (P = 0.0154);Loss of MoRF binding (P = 0.0154);
MVP		0.82
MPC		0.80
ClinPred		0.97	D
GERP RS		3.1
Varity_R		0.42
gMVP		0.92

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-72434479;