rs7249094

Variant names:

• chr19-8607115-G-A
• rs7249094
• NM_030957.4:c.-100+1019C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-8607115-G-A
• chr19-8607115-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030957.4(ADAMTS10):​c.-100+1019C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,678 control chromosomes in the GnomAD database, including 16,517 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 0.45 (16517 hom., cov: 30)
• Consequence: ADAMTS10 NM_030957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 17 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS10	NM_030957.4	c.-100+1019C>T		intron_variant	Intron 2 of 25	ENST00000597188.6	NP_112219.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS10	ENST00000597188.6	c.-100+1019C>T		intron_variant	Intron 2 of 25	5	NM_030957.4	ENSP00000471851.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 68929 AN: 151560 Hom.: 16508 Cov.: 30

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.453

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.455 AC: 68979 AN: 151678 Hom.: 16517 Cov.: 30 AF XY: 0.461 AC XY: 34141 AN XY: 74088

African (AFR) AF: 0.517 AC: 21400 AN: 41372

American (AMR) AF: 0.455 AC: 6931 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1877 AN: 3468

East Asian (EAS) AF: 0.901 AC: 4608 AN: 5114

South Asian (SAS) AF: 0.591 AC: 2838 AN: 4802

European-Finnish (FIN) AF: 0.376 AC: 3958 AN: 10520

Middle Eastern (MID) AF: 0.438 AC: 127 AN: 290

European-Non Finnish (NFE) AF: 0.383 AC: 25985 AN: 67862

Other (OTH) AF: 0.449 AC: 949 AN: 2112

Alfa AF: 0.418 Hom.: 52935

Bravo AF: 0.461

Asia WGS AF: 0.697 AC: 2423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.41
PhyloP100		0.049
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: rs7249094; hg19: chr19-8672000;