Variant 19-8580807-G-GC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_030957.4(ADAMTS10):c.*85_*86insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,091,496 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0036 ( 12 hom. )

Consequence

ADAMTS10
NM_030957.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.200

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00303 (460/151792) while in subpopulation NFE AF= 0.0054 (366/67824). AF 95% confidence interval is 0.00494. There are 0 homozygotes in gnomad4. There are 206 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS10	NM_030957.4 linkuse as main transcript	c.85_86insG		3_prime_UTR_variant	26/26	ENST00000597188.6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS10	ENST00000597188.6 linkuse as main transcript	c.85_86insG	3_prime_UTR_variant	26/26	5	NM_030957.4	P1
ADAMTS10	ENST00000270328.8 linkuse as main transcript	c.85_86insG	3_prime_UTR_variant	25/25	5		P1
ADAMTS10	ENST00000595838.5 linkuse as main transcript	c.85_86insG	3_prime_UTR_variant	13/13	2			Q9H324-2
ADAMTS10	ENST00000593913.5 linkuse as main transcript	c.2274_2275insG	3_prime_UTR_variant, NMD_transcript_variant	22/22	5

Frequencies

GnomAD3 genomes

AF:

0.00303

AC:

460

AN:

151676

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000630

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00530

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00540

Gnomad OTH

AF:

0.000961

GnomAD4 exome

AF:

0.00363

AC:

3414

AN:

939704

Hom.:

Cov.:

AF XY:

0.00346

AC XY:

1660

AN XY:

479570

show subpopulations

Gnomad4 AFR exome

AF:

0.000990

Gnomad4 AMR exome

AF:

0.000316

Gnomad4 ASJ exome

AF:

0.0000959

Gnomad4 EAS exome

AF:

0.000121

Gnomad4 SAS exome

AF:

0.000904

Gnomad4 FIN exome

AF:

0.00495

Gnomad4 NFE exome

AF:

0.00446

Gnomad4 OTH exome

AF:

0.00227

GnomAD4 genome

AF:

0.00303

AC:

460

AN:

151792

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

206

AN XY:

74176

show subpopulations

Gnomad4 AFR

AF:

0.000628

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00530

Gnomad4 NFE

AF:

0.00540

Gnomad4 OTH

AF:

0.000951

Bravo

AF:

0.00247

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Weill-Marchesani syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over