Genetic Variant ADAMTSL5:p.Arg467Trp (chr19-1506032-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_213604.3(ADAMTSL5):c.1399C>T(p.Arg467Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00622 in 1,578,142 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0063 ( 37 hom. )

Consequence

ADAMTSL5
NM_213604.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.446

Variant links:

Genes affected

ADAMTSL5 (HGNC:27912): (ADAMTS like 5) Enables heparin binding activity and microfibril binding activity. Located in extracellular region and microfibril. [provided by Alliance of Genome Resources, Apr 2022]

ADAMTSL5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054112077).

BP6

Variant 19-1506032-G-A is Benign according to our data. Variant chr19-1506032-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648938.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL5	NM_213604.3 link	c.1399C>T	p.Arg467Trp	missense_variant	Exon 12 of 12	ENST00000330475.9	NP_998769.2	Q6ZMM2Q0VD77X6R4H8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL5	ENST00000330475.9 link	c.1399C>T	p.Arg467Trp	missense_variant	Exon 12 of 12	2	NM_213604.3	ENSP00000327608.3		X6R4H8

Frequencies

GnomAD3 genomes

AF:

0.00518

AC:

789

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00510

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00838

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00775

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00508

AC:

1032

AN:

203232

Hom.:

AF XY:

0.00494

AC XY:

552

AN XY:

111740

show subpopulations

Gnomad AFR exome

AF:

0.00145

Gnomad AMR exome

AF:

0.00316

Gnomad ASJ exome

AF:

0.00188

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00353

Gnomad FIN exome

AF:

0.0106

Gnomad NFE exome

AF:

0.00713

Gnomad OTH exome

AF:

0.00595

GnomAD4 exome

AF:

0.00633

AC:

9020

AN:

1425792

Hom.:

Cov.:

AF XY:

0.00615

AC XY:

4350

AN XY:

707788

show subpopulations

Gnomad4 AFR exome

AF:

0.00100

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.00204

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00379

Gnomad4 FIN exome

AF:

0.0110

Gnomad4 NFE exome

AF:

0.00690

Gnomad4 OTH exome

AF:

0.00719

GnomAD4 genome

AF:

0.00519

AC:

790

AN:

152350

Hom.:

Cov.:

AF XY:

0.00532

AC XY:

396

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00838

Gnomad4 NFE

AF:

0.00775

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00642

Hom.:

Bravo

AF:

0.00465

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00163

AC:

ESP6500EA

AF:

0.00510

AC:

ExAC

AF:

0.00467

AC:

557

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ADAMTSL5: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.97

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.17

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0020

Vest4

0.15

MVP

0.52

MPC

0.50

ClinPred

0.020

GERP RS

-2.5

gMVP

0.49

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