NM_080722.4:c.*1580A>G

Variant names:

• chr10-70762433-A-G
• rs3740434
• NM_080722.4:c.*1580A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080722.4(ADAMTS14):​c.*1580A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,164 control chromosomes in the GnomAD database, including 28,685 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 0.61 (28674 hom., cov: 34)
  • Exomes 𝑓: 0.58 (11 hom.)
• Consequence: ADAMTS14 NM_080722.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.*1580A>G		3_prime_UTR_variant	Exon 22 of 22	ENST00000373207.2	NP_542453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2	c.*1580A>G		3_prime_UTR_variant	Exon 22 of 22	1	NM_080722.4	ENSP00000362303.1
ADAMTS14	ENST00000373208.5	c.*1580A>G		3_prime_UTR_variant	Exon 22 of 22	2		ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92919 AN: 151986 Hom.: 28655 Cov.: 34

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.617

GnomAD4 exome AF: 0.583 AC: 35 AN: 60 Hom.: 11 Cov.: 0 AF XY: 0.571 AC XY: 24 AN XY: 42

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.611 AC: 92983 AN: 152104 Hom.: 28674 Cov.: 34 AF XY: 0.610 AC XY: 45356 AN XY: 74346

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.621

Alfa AF: 0.617 Hom.: 11782

Bravo AF: 0.599

Asia WGS AF: 0.713 AC: 2482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.8
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3740434; hg19: chr10-72522189;