19-8604988-C-T

Variant names:

• chr19-8604988-C-T
• rs7260282
• NM_030957.4:c.435+24G>A

Variant summary

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

The NM_030957.4(ADAMTS10):​c.435+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,571,508 control chromosomes in the GnomAD database, including 59,063 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 0.22 (4259 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54804 hom.)
• Consequence: ADAMTS10 NM_030957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS10	NM_030957.4	c.435+24G>A		intron_variant	Intron 4 of 25	ENST00000597188.6	NP_112219.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS10	ENST00000597188.6	c.435+24G>A		intron_variant	Intron 4 of 25	5	NM_030957.4	ENSP00000471851.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33714 AN: 152048 Hom.: 4262 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.0793

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.267 AC: 379371 AN: 1419342 Hom.: 54804 Cov.: 31 AF XY: 0.263 AC XY: 184809 AN XY: 703214

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.0353

Gnomad4 SAS exome AF: 0.0831

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.222 AC: 33706 AN: 152166 Hom.: 4259 Cov.: 32 AF XY: 0.218 AC XY: 16259 AN XY: 74412

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0396

Gnomad4 SAS AF: 0.0787

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.243

Alfa AF: 0.214 Hom.: 1104

Bravo AF: 0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7260282; hg19: chr19-8669873;