chr19-8604988-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

ADAMTS10 Gene-Disease associations (from GenCC):

• Weill-Marchesani syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Weill-Marchesani syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030957.4. 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
	ADAMTS10	NM_030957.4	MANE Select	c.435+24G>A		intron	N/A	NP_112219.3	A0A0A0MQW6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS10	ENST00000597188.6	TSL:5 MANE Select	c.435+24G>A		intron	N/A	ENSP00000471851.1	A0A0A0MQW6
	ADAMTS10	ENST00000270328.8	TSL:5	c.435+24G>A		intron	N/A	ENSP00000270328.4	A0A0A0MQW6
	ADAMTS10	ENST00000906412.1		c.435+24G>A		intron	N/A	ENSP00000576471.1

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

African (AFR) AF: 0.122 AC: 3931 AN: 32144

American (AMR) AF: 0.150 AC: 5711 AN: 37994

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 4782 AN: 25396

East Asian (EAS) AF: 0.0353 AC: 1304 AN: 36926

South Asian (SAS) AF: 0.0831 AC: 6790 AN: 81744

European-Finnish (FIN) AF: 0.308 AC: 15418 AN: 50078

Middle Eastern (MID) AF: 0.231 AC: 1323 AN: 5736

European-Non Finnish (NFE) AF: 0.299 AC: 325631 AN: 1090494

Other (OTH) AF: 0.246 AC: 14481 AN: 58830

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

African (AFR) AF: 0.128 AC: 5308 AN: 41526

American (AMR) AF: 0.195 AC: 2976 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3470

East Asian (EAS) AF: 0.0396 AC: 205 AN: 5180

South Asian (SAS) AF: 0.0787 AC: 380 AN: 4826

European-Finnish (FIN) AF: 0.306 AC: 3236 AN: 10592

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19969 AN: 67984

Other (OTH) AF: 0.243 AC: 514 AN: 2114

Alfa AF: 0.214 Hom.: 1104

Bravo AF: 0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.34
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs7260282; hg19: chr19-8669873;