Variant 15-83819884-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_207517.3(ADAMTSL3):c.437A>G(p.His146Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,613,496 control chromosomes in the GnomAD database, including 199,622 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.57 ( 26407 hom., cov: 30)

Exomes 𝑓: 0.48 ( 173215 hom. )

Consequence

ADAMTSL3
NM_207517.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.218

Variant links:

Genes affected

ADAMTSL3 (HGNC:14633): (ADAMTS like 3) Predicted to be involved in extracellular matrix organization. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ADAMTSL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2363032E-6).

BP6

Variant 15-83819884-A-G is Benign according to our data. Variant chr15-83819884-A-G is described in ClinVar as [Benign]. Clinvar id is 1243188.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL3	NM_207517.3 linkuse as main transcript	c.437A>G	p.His146Arg	missense_variant	6/30	ENST00000286744.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL3	ENST00000286744.10 linkuse as main transcript	c.437A>G	p.His146Arg	missense_variant	6/30	1	NM_207517.3	P1	P82987-1

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86768

AN:

151764

Hom.:

26371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.772

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.531

Gnomad ASJ

AF:

0.522

Gnomad EAS

AF:

0.797

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.490

Gnomad MID

AF:

0.634

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.557

GnomAD3 exomes

AF:

0.536

AC:

134591

AN:

251190

Hom.:

37936

AF XY:

0.533

AC XY:

72393

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.780

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.518

Gnomad EAS exome

AF:

0.797

Gnomad SAS exome

AF:

0.635

Gnomad FIN exome

AF:

0.490

Gnomad NFE exome

AF:

0.449

Gnomad OTH exome

AF:

0.506

GnomAD4 exome

AF:

0.478

AC:

698630

AN:

1461614

Hom.:

173215

Cov.:

AF XY:

0.482

AC XY:

350185

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.781

Gnomad4 AMR exome

AF:

0.522

Gnomad4 ASJ exome

AF:

0.514

Gnomad4 EAS exome

AF:

0.790

Gnomad4 SAS exome

AF:

0.634

Gnomad4 FIN exome

AF:

0.486

Gnomad4 NFE exome

AF:

0.440

Gnomad4 OTH exome

AF:

0.510

GnomAD4 genome

AF:

0.572

AC:

86864

AN:

151882

Hom.:

26407

Cov.:

AF XY:

0.576

AC XY:

42744

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.772

Gnomad4 AMR

AF:

0.532

Gnomad4 ASJ

AF:

0.522

Gnomad4 EAS

AF:

0.797

Gnomad4 SAS

AF:

0.641

Gnomad4 FIN

AF:

0.490

Gnomad4 NFE

AF:

0.453

Gnomad4 OTH

AF:

0.556

Alfa

AF:

0.481

Hom.:

44395

Bravo

AF:

0.581

TwinsUK

AF:

0.434

AC:

1611

ALSPAC

AF:

0.449

AC:

1731

ESP6500AA

AF:

0.762

AC:

3358

ESP6500EA

AF:

0.460

AC:

3958

ExAC

AF:

0.540

AC:

65518

Asia WGS

AF:

0.716

AC:

2490

AN:

3478

EpiCase

AF:

0.459

EpiControl

AF:

0.457

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

Cadd

Benign

0.038

Dann

Benign

0.44

DEOGEN2

Benign

0.0042

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.024

T;T

MetaRNN

Benign

0.0000012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.65

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.46

N;N

REVEL

Benign

0.10

Sift

Benign

0.38

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.0050

MPC

0.15

ClinPred

0.0080

GERP RS

-3.4

Varity_R

0.033

gMVP

0.33

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