12-43376124-C-A

Variant names:

• chr12-43376124-C-A
• NM_025003.5:c.5245G>T

Variant summary

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

The NM_025003.5(ADAMTS20):​c.5245G>T​(p.Glu1749*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ADAMTS20 NM_025003.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

Genes affected

ADAMTS20 (HGNC:17178): (ADAM metallopeptidase with thrombospondin type 1 motif 20) The protein encoded by this gene is a member of the ADAMTS family of zinc-dependent proteases. The encoded protein has a signal peptide that is cleaved to release the mature peptide, which is secreted and found in the extracellular matrix. This protein may be involved in tissue remodeling. [provided by RefSeq, Sep 2011]

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
ADAMTS20	NM_025003.5	c.5245G>T	p.Glu1749*	stop_gained	Exon 35 of 39	ENST00000389420.8	NP_079279.3
ADAMTS20	XM_011538754.3	c.5248G>T	p.Glu1750*	stop_gained	Exon 35 of 39		XP_011537056.1
ADAMTS20	XM_017019979.2	c.4033G>T	p.Glu1345*	stop_gained	Exon 28 of 32		XP_016875468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS20	ENST00000389420.8	c.5245G>T	p.Glu1749*	stop_gained	Exon 35 of 39	1	NM_025003.5	ENSP00000374071.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457030 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724214

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: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	0.80
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.93	D
Vest4		0.32
GERP RS		3.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.53		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.53		Position offset: 24

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: chr12-43769927;