chr19-8580436-AC-A

Position:

• chr19-8580436-AC-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_030957.4(ADAMTS10):​c.*456del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (19989 hom., cov: 0)
  • Exomes 𝑓: 0.45 (934 hom.)
• Consequence: ADAMTS10 NM_030957.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.262

Genes affected

ADAMTS10 (HGNC:13201): (ADAM metallopeptidase with thrombospondin type 1 motif 10) This gene belongs to the ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin type-1 motifs) family of zinc-dependent proteases. ADAMTS proteases are complex secreted enzymes containing a prometalloprotease domain of the reprolysin type attached to an ancillary domain with a highly conserved structure that includes at least one thrombospondin type 1 repeat. They have been demonstrated to have important roles in connective tissue organization, coagulation, inflammation, arthritis, angiogenesis and cell migration. The product of this gene plays a major role in growth and in skin, lens, and heart development. It is also a candidate gene for autosomal recessive Weill-Marchesani syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS10	NM_030957.4	c.*456del		3_prime_UTR_variant	26/26	ENST00000597188.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS10	ENST00000597188.6	c.*456del		3_prime_UTR_variant	26/26	5	NM_030957.4	P1
ADAMTS10	ENST00000270328.8	c.*456del		3_prime_UTR_variant	25/25	5		P1
ADAMTS10	ENST00000595838.5	c.*456del		3_prime_UTR_variant	13/13	2

Frequencies

GnomAD3 genomes AF: 0.545 AC: 76531 AN: 140528 Hom.: 19979 Cov.: 0

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.575

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.550

GnomAD4 exome AF: 0.447 AC: 4842 AN: 10834 Hom.: 934 Cov.: 0 AF XY: 0.462 AC XY: 2869 AN XY: 6210

Gnomad4 AFR exome AF: 0.463

Gnomad4 AMR exome AF: 0.527

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.676

Gnomad4 SAS exome AF: 0.489

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.402

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.545 AC: 76577 AN: 140604 Hom.: 19989 Cov.: 0 AF XY: 0.553 AC XY: 37902 AN XY: 68524

Gnomad4 AFR AF: 0.568

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.553

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Weill-Marchesani syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

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: rs34057037; hg19: chr19-8645320;