Variant rs950169 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 ENST00000286744.10(ADAMTSL3):c.4979C>T(p.Thr1660Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,601,146 control chromosomes in the GnomAD database, including 51,901 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 0.19 ( 3670 hom., cov: 33)

Exomes 𝑓: 0.25 ( 48231 hom. )

Consequence

ADAMTSL3
ENST00000286744.10 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.54

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=0.005163908).

BP6

Variant 15-84037709-C-T is Benign according to our data. Variant chr15-84037709-C-T is described in ClinVar as [Benign]. Clinvar id is 1268691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3 linkuse as main transcript	c.4979C>T	p.Thr1660Ile	missense_variant	30/30	ENST00000286744.10	NP_997400.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTSL3	ENST00000286744.10 linkuse as main transcript	c.4979C>T	p.Thr1660Ile	missense_variant	30/30	1	NM_207517.3	ENSP00000286744	P1	P82987-1
ADAMTSL3	ENST00000567476.1 linkuse as main transcript	c.4987-54C>T		intron_variant		1		ENSP00000456313		P82987-2

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29376

AN:

152098

Hom.:

3670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0459

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.0529

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.211

GnomAD3 exomes

AF:

0.222

AC:

53411

AN:

240738

Hom.:

6762

AF XY:

0.230

AC XY:

29949

AN XY:

129938

show subpopulations

Gnomad AFR exome

AF:

0.0409

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.0475

Gnomad SAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.277

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.251

AC:

363272

AN:

1448930

Hom.:

48231

Cov.:

AF XY:

0.252

AC XY:

181539

AN XY:

720624

show subpopulations

Gnomad4 AFR exome

AF:

0.0395

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.257

Gnomad4 EAS exome

AF:

0.0440

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.252

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.193

AC:

29373

AN:

152216

Hom.:

3670

Cov.:

AF XY:

0.192

AC XY:

14316

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0458

Gnomad4 AMR

AF:

0.198

Gnomad4 ASJ

AF:

0.260

Gnomad4 EAS

AF:

0.0526

Gnomad4 SAS

AF:

0.211

Gnomad4 FIN

AF:

0.259

Gnomad4 NFE

AF:

0.272

Gnomad4 OTH

AF:

0.209

Alfa

AF:

0.259

Hom.:

13588

Bravo

AF:

0.183

TwinsUK

AF:

0.269

AC:

998

ALSPAC

AF:

0.259

AC:

998

ESP6500AA

AF:

0.0477

AC:

210

ESP6500EA

AF:

0.270

AC:

2323

ExAC

AF:

0.221

AC:

26844

Asia WGS

AF:

0.141

AC:

492

AN:

3478

EpiCase

AF:

0.289

EpiControl

AF:

0.288

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	This variant is associated with the following publications: (PMID: 19197363, 21239144) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0078

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.4

REVEL

Benign

0.12

Sift

Benign

0.055

Sift4G

Uncertain

0.027

Polyphen

0.0

Vest4

0.028

MPC

0.13

ClinPred

0.023

GERP RS

-0.022

Varity_R

0.12

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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