chr19-8580654-A-AG

Variant names:

• chr19-8580654-A-AG
• rs151216219
• NM_030957.4:c.*238dupC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_030957.4(ADAMTS10):​c.*238dupC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 506,206 control chromosomes in the GnomAD database, including 2,958 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.096 (813 hom., cov: 29)
  • Exomes 𝑓: 0.10 (2145 hom.)
• Consequence: ADAMTS10 NM_030957.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.89
• Publications: 0 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 -16 ACMG points.

• BP6: Variant 19-8580654-A-AG is Benign according to our data. Variant chr19-8580654-A-AG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 330572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.126 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.*238dupC		3_prime_UTR	Exon 26 of 26	NP_112219.3	A0A0A0MQW6
	ADAMTS10	NM_001282352.2		c.*238dupC		3_prime_UTR	Exon 13 of 13	NP_001269281.1	Q9H324-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS10	ENST00000597188.6	TSL:5 MANE Select	c.*238dupC		3_prime_UTR	Exon 26 of 26	ENSP00000471851.1	A0A0A0MQW6
	ADAMTS10	ENST00000270328.8	TSL:5	c.*238dupC		3_prime_UTR	Exon 25 of 25	ENSP00000270328.4	A0A0A0MQW6
	ADAMTS10	ENST00000906412.1		c.*238dupC		3_prime_UTR	Exon 25 of 25	ENSP00000576471.1

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14551 AN: 151178 Hom.: 808 Cov.: 29

Gnomad AFR AF: 0.0445

Gnomad AMI AF: 0.0551

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0433

Gnomad EAS AF: 0.0598

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0919

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.0894

GnomAD4 exome AF: 0.105 AC: 37249 AN: 354908 Hom.: 2145 Cov.: 1 AF XY: 0.103 AC XY: 19480 AN XY: 189260

African (AFR) AF: 0.0412 AC: 407 AN: 9868

American (AMR) AF: 0.140 AC: 2153 AN: 15376

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 481 AN: 10438

East Asian (EAS) AF: 0.0532 AC: 1219 AN: 22902

South Asian (SAS) AF: 0.0854 AC: 3812 AN: 44642

European-Finnish (FIN) AF: 0.0931 AC: 1914 AN: 20566

Middle Eastern (MID) AF: 0.0737 AC: 107 AN: 1452

European-Non Finnish (NFE) AF: 0.120 AC: 25195 AN: 209744

Other (OTH) AF: 0.0984 AC: 1961 AN: 19920

GnomAD4 genome AF: 0.0963 AC: 14569 AN: 151298 Hom.: 813 Cov.: 29 AF XY: 0.0946 AC XY: 6996 AN XY: 73918

African (AFR) AF: 0.0445 AC: 1835 AN: 41228

American (AMR) AF: 0.130 AC: 1973 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.0433 AC: 150 AN: 3468

East Asian (EAS) AF: 0.0590 AC: 300 AN: 5088

South Asian (SAS) AF: 0.0897 AC: 429 AN: 4782

European-Finnish (FIN) AF: 0.0919 AC: 966 AN: 10514

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8660 AN: 67708

Other (OTH) AF: 0.0885 AC: 186 AN: 2102

Alfa AF: 0.0371 Hom.: 44

Bravo AF: 0.0945

Asia WGS AF: 0.0700 AC: 245 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Weill-Marchesani syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.9
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

Other links and lift over

dbSNP: rs151216219; hg19: chr19-8645538;