10-70762433-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080722.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	NM_080722.4	MANE Select	c.*1580A>G		3_prime_UTR	Exon 22 of 22	NP_542453.2	Q8WXS8-1
	ADAMTS14	NM_139155.3		c.*1580A>G		3_prime_UTR	Exon 22 of 22	NP_631894.2	Q8WXS8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	ENST00000373207.2	TSL:1 MANE Select	c.*1580A>G		3_prime_UTR	Exon 22 of 22	ENSP00000362303.1	Q8WXS8-1
	ADAMTS14	ENST00000886732.1		c.*1580A>G		3_prime_UTR	Exon 22 of 22	ENSP00000556791.1
	ADAMTS14	ENST00000373208.5	TSL:2	c.*1580A>G		3_prime_UTR	Exon 22 of 22	ENSP00000362304.1	Q8WXS8-4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.680 AC: 34 AN: 50

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.575 AC: 23847 AN: 41468

American (AMR) AF: 0.530 AC: 8101 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1900 AN: 3472

East Asian (EAS) AF: 0.698 AC: 3601 AN: 5158

South Asian (SAS) AF: 0.682 AC: 3296 AN: 4830

European-Finnish (FIN) AF: 0.619 AC: 6550 AN: 10576

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43559 AN: 67984

Other (OTH) AF: 0.621 AC: 1313 AN: 2116

Alfa AF: 0.614 Hom.: 14044

Bravo AF: 0.599

Asia WGS AF: 0.713 AC: 2482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3740434; hg19: chr10-72522189;