chr19-8580444-C-G

Position:

chr19-8580444-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_030957.4(ADAMTS10):c.*449G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 171,314 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 28 hom., cov: 30)

Exomes 𝑓: 0.011 ( 5 hom. )

Consequence

ADAMTS10
NM_030957.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.10

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 19-8580444-C-G is Benign according to our data. Variant chr19-8580444-C-G is described in ClinVar as [Benign]. Clinvar id is 330568.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0147 (2227/151820) while in subpopulation AMR AF= 0.0236 (360/15270). AF 95% confidence interval is 0.0216. There are 28 homozygotes in gnomad4. There are 1035 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS10	NM_030957.4 linkuse as main transcript	c.*449G>C		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.*449G>C	3_prime_UTR_variant	26/26	5	NM_030957.4	P1
ADAMTS10	ENST00000270328.8 linkuse as main transcript	c.*449G>C	3_prime_UTR_variant	25/25	5		P1
ADAMTS10	ENST00000595838.5 linkuse as main transcript	c.*449G>C	3_prime_UTR_variant	13/13	2			Q9H324-2

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2229

AN:

151702

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00417

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0237

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.0200

Gnomad SAS

AF:

0.00560

Gnomad FIN

AF:

0.00915

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0201

Gnomad OTH

AF:

0.0292

GnomAD4 exome

AF:

0.0113

AC:

220

AN:

19494

Hom.:

Cov.:

AF XY:

0.00989

AC XY:

110

AN XY:

11126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0175

Gnomad4 ASJ exome

AF:

0.0137

Gnomad4 EAS exome

AF:

0.0114

Gnomad4 SAS exome

AF:

0.00298

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.0137

Gnomad4 OTH exome

AF:

0.00996

GnomAD4 genome

AF:

0.0147

AC:

2227

AN:

151820

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1035

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.00416

Gnomad4 AMR

AF:

0.0236

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.0199

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.00915

Gnomad4 NFE

AF:

0.0201

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.00310

Hom.:

Bravo

AF:

0.0157

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Weill-Marchesani syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.66

DANN

Benign

0.22

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