rs116024095

Variant names:

• chr19-8580465-T-C
• rs116024095
• NM_030957.4:c.*428A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-8580465-T-C
• chr19-8580465-T-A
• chr19-8580465-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030957.4(ADAMTS10):​c.*428A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 169,020 control chromosomes in the GnomAD database, including 1,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (1149 hom., cov: 30)
  • Exomes 𝑓: 0.0074 (7 hom.)
• Consequence: ADAMTS10 NM_030957.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.338
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-8580465-T-C is Benign according to our data. Variant chr19-8580465-T-C is described in ClinVar as Benign. ClinVar VariationId is 330569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 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.*428A>G		3_prime_UTR	Exon 26 of 26	NP_112219.3	A0A0A0MQW6
	ADAMTS10	NM_001282352.2		c.*428A>G		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.*428A>G		3_prime_UTR	Exon 26 of 26	ENSP00000471851.1	A0A0A0MQW6
	ADAMTS10	ENST00000270328.8	TSL:5	c.*428A>G		3_prime_UTR	Exon 25 of 25	ENSP00000270328.4	A0A0A0MQW6
	ADAMTS10	ENST00000906412.1		c.*428A>G		3_prime_UTR	Exon 25 of 25	ENSP00000576471.1

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11021 AN: 150728 Hom.: 1149 Cov.: 30

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0177

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.00670

Gnomad FIN AF: 0.00250

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0545

GnomAD4 exome AF: 0.00737 AC: 134 AN: 18176 Hom.: 7 Cov.: 0 AF XY: 0.00745 AC XY: 79 AN XY: 10608

African (AFR) AF: 0.161 AC: 29 AN: 180

American (AMR) AF: 0.0189 AC: 29 AN: 1538

Ashkenazi Jewish (ASJ) AF: 0.00368 AC: 1 AN: 272

East Asian (EAS) AF: 0.00313 AC: 2 AN: 640

South Asian (SAS) AF: 0.00375 AC: 15 AN: 4000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1010

Middle Eastern (MID) AF: 0.0926 AC: 5 AN: 54

European-Non Finnish (NFE) AF: 0.00485 AC: 47 AN: 9688

Other (OTH) AF: 0.00756 AC: 6 AN: 794

GnomAD4 genome AF: 0.0733 AC: 11050 AN: 150844 Hom.: 1149 Cov.: 30 AF XY: 0.0717 AC XY: 5289 AN XY: 73754

African (AFR) AF: 0.234 AC: 9575 AN: 40938

American (AMR) AF: 0.0310 AC: 472 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0177 AC: 61 AN: 3452

East Asian (EAS) AF: 0.0139 AC: 71 AN: 5110

South Asian (SAS) AF: 0.00650 AC: 31 AN: 4772

European-Finnish (FIN) AF: 0.00250 AC: 26 AN: 10410

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 688 AN: 67642

Other (OTH) AF: 0.0563 AC: 118 AN: 2096

Alfa AF: 0.00642 Hom.: 7

Bravo AF: 0.0831

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.66
PhyloP100		-0.34
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: rs116024095; hg19: chr19-8645349;