Variant 15-83913372-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_207517.3(ADAMTSL3):c.1981G>T(p.Val661Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,611,870 control chromosomes in the GnomAD database, including 255,803 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.63 ( 31001 hom., cov: 31)

Exomes 𝑓: 0.55 ( 224802 hom. )

Consequence

ADAMTSL3
NM_207517.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.250

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.850039E-7).

BP6

Variant 15-83913372-G-T is Benign according to our data. Variant chr15-83913372-G-T is described in ClinVar as [Benign]. Clinvar id is 1273050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3 link	c.1981G>T	p.Val661Leu	missense_variant	16/30	ENST00000286744.10	NP_997400.2	P82987-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADAMTSL3	ENST00000286744.10 link	c.1981G>T	p.Val661Leu	missense_variant	16/30	1	NM_207517.3	ENSP00000286744.5	P82987-1
ADAMTSL3	ENST00000567476.1 link	c.1981G>T	p.Val661Leu	missense_variant	16/30	1		ENSP00000456313.1	P82987-2
ADAMTSL3	ENST00000561483.5 link	n.2196G>T		non_coding_transcript_exon_variant	16/27	5

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

95235

AN:

151922

Hom.:

30953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.787

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.708

Gnomad ASJ

AF:

0.617

Gnomad EAS

AF:

0.744

Gnomad SAS

AF:

0.613

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.668

Gnomad NFE

AF:

0.523

Gnomad OTH

AF:

0.617

GnomAD3 exomes

AF:

0.607

AC:

149827

AN:

246792

Hom.:

47183

AF XY:

0.595

AC XY:

79447

AN XY:

133544

show subpopulations

Gnomad AFR exome

AF:

0.793

Gnomad AMR exome

AF:

0.794

Gnomad ASJ exome

AF:

0.614

Gnomad EAS exome

AF:

0.744

Gnomad SAS exome

AF:

0.603

Gnomad FIN exome

AF:

0.512

Gnomad NFE exome

AF:

0.520

Gnomad OTH exome

AF:

0.569

GnomAD4 exome

AF:

0.550

AC:

802953

AN:

1459830

Hom.:

224802

Cov.:

AF XY:

0.550

AC XY:

399327

AN XY:

726160

show subpopulations

Gnomad4 AFR exome

AF:

0.798

Gnomad4 AMR exome

AF:

0.784

Gnomad4 ASJ exome

AF:

0.607

Gnomad4 EAS exome

AF:

0.726

Gnomad4 SAS exome

AF:

0.609

Gnomad4 FIN exome

AF:

0.509

Gnomad4 NFE exome

AF:

0.521

Gnomad4 OTH exome

AF:

0.572

GnomAD4 genome

AF:

0.627

AC:

95345

AN:

152040

Hom.:

31001

Cov.:

AF XY:

0.628

AC XY:

46703

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.787

Gnomad4 AMR

AF:

0.708

Gnomad4 ASJ

AF:

0.617

Gnomad4 EAS

AF:

0.744

Gnomad4 SAS

AF:

0.613

Gnomad4 FIN

AF:

0.512

Gnomad4 NFE

AF:

0.523

Gnomad4 OTH

AF:

0.616

Alfa

AF:

0.548

Hom.:

54506

Bravo

AF:

0.650

TwinsUK

AF:

0.516

AC:

1914

ALSPAC

AF:

0.539

AC:

2076

ESP6500AA

AF:

0.776

AC:

3420

ESP6500EA

AF:

0.537

AC:

4620

ExAC

AF:

0.598

AC:

72562

Asia WGS

AF:

0.673

AC:

2341

AN:

3478

EpiCase

AF:

0.528

EpiControl

AF:

0.530

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.6

DANN

Benign

0.91

DEOGEN2

Benign

0.012

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.080

T;T

MetaRNN

Benign

5.9e-7

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.4

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

0.22

N;N

REVEL

Benign

0.19

Sift

Benign

0.23

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.0

B;B

Vest4

0.034

MutPred

0.76

Loss of glycosylation at T659 (P = 0.1653);Loss of glycosylation at T659 (P = 0.1653);

MPC

0.12

ClinPred

0.0028

GERP RS

-1.8

Varity_R

0.058

gMVP

0.21

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