10-70741107-C-G

Variant names:

• chr10-70741107-C-G
• rs10999500
• NM_080722.4:c.1869C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_080722.4(ADAMTS14):​c.1869C>G​(p.Ser623Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,613,710 control chromosomes in the GnomAD database, including 303,385 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 0.63 (30522 hom., cov: 33)
  • Exomes 𝑓: 0.61 (272863 hom.)
• Consequence: ADAMTS14 NM_080722.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524
• Publications: 16 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=0.524 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.1869C>G	p.Ser623Ser	synonymous_variant	Exon 12 of 22	ENST00000373207.2	NP_542453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2	c.1869C>G	p.Ser623Ser	synonymous_variant	Exon 12 of 22	1	NM_080722.4	ENSP00000362303.1
ADAMTS14	ENST00000373208.5	c.1878C>G	p.Ser626Ser	synonymous_variant	Exon 12 of 22	2		ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95919 AN: 152020 Hom.: 30501 Cov.: 33

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.611

GnomAD2 exomes AF: 0.628 AC: 157775 AN: 251038 AF XY: 0.628

Gnomad AFR exome AF: 0.658

Gnomad AMR exome AF: 0.552

Gnomad ASJ exome AF: 0.677

Gnomad EAS exome AF: 0.867

Gnomad FIN exome AF: 0.685

Gnomad NFE exome AF: 0.598

Gnomad OTH exome AF: 0.618

GnomAD4 exome AF: 0.609 AC: 889763 AN: 1461572 Hom.: 272863 Cov.: 69 AF XY: 0.610 AC XY: 443283 AN XY: 727080

African (AFR) AF: 0.663 AC: 22207 AN: 33480

American (AMR) AF: 0.555 AC: 24820 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 17660 AN: 26136

East Asian (EAS) AF: 0.863 AC: 34273 AN: 39698

South Asian (SAS) AF: 0.618 AC: 53344 AN: 86254

European-Finnish (FIN) AF: 0.682 AC: 36296 AN: 53190

Middle Eastern (MID) AF: 0.614 AC: 3540 AN: 5766

European-Non Finnish (NFE) AF: 0.593 AC: 659940 AN: 1111952

Other (OTH) AF: 0.624 AC: 37683 AN: 60384

GnomAD4 genome AF: 0.631 AC: 95991 AN: 152138 Hom.: 30522 Cov.: 33 AF XY: 0.636 AC XY: 47300 AN XY: 74388

African (AFR) AF: 0.662 AC: 27472 AN: 41496

American (AMR) AF: 0.578 AC: 8840 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2348 AN: 3470

East Asian (EAS) AF: 0.870 AC: 4497 AN: 5168

South Asian (SAS) AF: 0.627 AC: 3027 AN: 4830

European-Finnish (FIN) AF: 0.690 AC: 7317 AN: 10600

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40672 AN: 67970

Other (OTH) AF: 0.613 AC: 1296 AN: 2114

Alfa AF: 0.565 Hom.: 3164

Bravo AF: 0.621

Asia WGS AF: 0.719 AC: 2495 AN: 3478

EpiCase AF: 0.600

EpiControl AF: 0.595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.7
DANN	Benign	0.69
PhyloP100		0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10999500; hg19: chr10-72500863;