10-70741107-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_080722.4(ADAMTS14):c.1869C>G(p.Ser623=) 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

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 Benign. Variant got -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/exons	MANE	UniProt
ADAMTS14	NM_080722.4	c.1869C>G	p.Ser623=	synonymous_variant	12/22	ENST00000373207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS14	ENST00000373207.2	c.1869C>G	p.Ser623=	synonymous_variant	12/22	1	NM_080722.4	P4
ADAMTS14	ENST00000373208.5	c.1878C>G	p.Ser626=	synonymous_variant	12/22	2		A2

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

GnomAD3 exomes AF: 0.628 AC: 157775 AN: 251038 Hom.: 50348 AF XY: 0.628 AC XY: 85259 AN XY: 135736

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 SAS exome AF: 0.616

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

Gnomad4 AFR exome AF: 0.663

Gnomad4 AMR exome AF: 0.555

Gnomad4 ASJ exome AF: 0.676

Gnomad4 EAS exome AF: 0.863

Gnomad4 SAS exome AF: 0.618

Gnomad4 FIN exome AF: 0.682

Gnomad4 NFE exome AF: 0.593

Gnomad4 OTH exome AF: 0.624

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

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.613

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs10999500; hg19: chr10-72500863;