Variant rs2277849 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.2605C>T(p.Leu869Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,613,688 control chromosomes in the GnomAD database, including 55,875 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.28 ( 6394 hom., cov: 32)

Exomes 𝑓: 0.25 ( 49481 hom. )

Consequence

ADAMTSL3
NM_207517.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.811

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:

ADAMTSL3 (HGNC:):

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=0.0047180355).

BP6

Variant 15-83970598-C-T is Benign according to our data. Variant chr15-83970598-C-T is described in ClinVar as [Benign]. Clinvar id is 1233330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 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.2605C>T	p.Leu869Phe	missense_variant	20/30	ENST00000286744.10	NP_997400.2	P82987-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTSL3	ENST00000286744.10 linkuse as main transcript	c.2605C>T	p.Leu869Phe	missense_variant	20/30	1	NM_207517.3	ENSP00000286744.5		P82987-1

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42859

AN:

152008

Hom.:

6395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.178

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.242

AC:

60782

AN:

251324

Hom.:

8313

AF XY:

0.236

AC XY:

32023

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.350

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.333

Gnomad SAS exome

AF:

0.104

Gnomad FIN exome

AF:

0.345

Gnomad NFE exome

AF:

0.264

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.255

AC:

372335

AN:

1461562

Hom.:

49481

Cov.:

AF XY:

0.250

AC XY:

182090

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.355

Gnomad4 AMR exome

AF:

0.132

Gnomad4 ASJ exome

AF:

0.242

Gnomad4 EAS exome

AF:

0.313

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.350

Gnomad4 NFE exome

AF:

0.262

Gnomad4 OTH exome

AF:

0.256

GnomAD4 genome

AF:

0.282

AC:

42880

AN:

152126

Hom.:

6394

Cov.:

AF XY:

0.280

AC XY:

20802

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.349

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.349

Gnomad4 NFE

AF:

0.267

Gnomad4 OTH

AF:

0.256

Alfa

AF:

0.262

Hom.:

13173

Bravo

AF:

0.276

TwinsUK

AF:

0.263

AC:

977

ALSPAC

AF:

0.265

AC:

1021

ESP6500AA

AF:

0.349

AC:

1537

ESP6500EA

AF:

0.264

AC:

2269

ExAC

AF:

0.246

AC:

29864

Asia WGS

AF:

0.193

AC:

672

AN:

3478

EpiCase

AF:

0.259

EpiControl

AF:

0.256

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0082

T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.75

T;T

MetaRNN

Benign

0.0047

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

M;M

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.13

Sift

Benign

0.077

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.79

P;P

Vest4

0.012

MPC

0.39

ClinPred

0.045

GERP RS

2.4

Varity_R

0.14

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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