Variant chr12-43376634-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000389420.8(ADAMTS20):c.5015T>C(p.Ile1672Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 1,612,568 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

ADAMTS20
ENST00000389420.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.199

Variant links:

Genes affected

ADAMTS20 (HGNC:17178): (ADAM metallopeptidase with thrombospondin type 1 motif 20) The protein encoded by this gene is a member of the ADAMTS family of zinc-dependent proteases. The encoded protein has a signal peptide that is cleaved to release the mature peptide, which is secreted and found in the extracellular matrix. This protein may be involved in tissue remodeling. [provided by RefSeq, Sep 2011]

ADAMTS20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040868968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADAMTS20	NM_025003.5 linkuse as main transcript	c.5015T>C	p.Ile1672Thr	missense_variant	33/39	ENST00000389420.8	NP_079279.3
ADAMTS20	XM_011538754.3 linkuse as main transcript	c.5018T>C	p.Ile1673Thr	missense_variant	33/39		XP_011537056.1
ADAMTS20	XM_017019979.2 linkuse as main transcript	c.3803T>C	p.Ile1268Thr	missense_variant	26/32		XP_016875468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS20	ENST00000389420.8 linkuse as main transcript	c.5015T>C	p.Ile1672Thr	missense_variant	33/39	1	NM_025003.5	ENSP00000374071	P1	P59510-3

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000209

AC:

AN:

249292

Hom.:

AF XY:

0.000178

AC XY:

AN XY:

134714

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000425

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000297

AC:

433

AN:

1460366

Hom.:

Cov.:

AF XY:

0.000301

AC XY:

219

AN XY:

726404

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000368

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000204

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00191

Alfa

AF:

0.000297

Hom.:

Bravo

AF:

0.000223

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000264

AC:

EpiCase

AF:

0.000492

EpiControl

AF:

0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.5015T>C (p.I1672T) alteration is located in exon 33 (coding exon 33) of the ADAMTS20 gene. This alteration results from a T to C substitution at nucleotide position 5015, causing the isoleucine (I) at amino acid position 1672 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.4

DANN

Benign

0.70

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.43

M_CAP

Benign

0.0035

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.2

REVEL

Benign

0.092

Sift

Benign

0.48

Sift4G

Benign

0.57

Vest4

0.17

MVP

0.37

MPC

0.040

ClinPred

0.019

GERP RS

-6.1

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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