dbSNP rs2277849: ADAMTSL3:p.Leu869Phe (chr15-83970598-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

36 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3 link	c.2605C>T	p.Leu869Phe	missense_variant	Exon 20 of 30	ENST00000286744.10	NP_997400.2	P82987-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL3	ENST00000286744.10 link	c.2605C>T	p.Leu869Phe	missense_variant	Exon 20 of 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

GnomAD2 exomes

AF:

0.242

AC:

60782

AN:

251324

AF XY:

0.236

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 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

African (AFR)

AF:

0.355

AC:

11880

AN:

33472

American (AMR)

AF:

0.132

AC:

5895

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

6336

AN:

26128

East Asian (EAS)

AF:

0.313

AC:

12444

AN:

39698

South Asian (SAS)

AF:

0.108

AC:

9308

AN:

86250

European-Finnish (FIN)

AF:

0.350

AC:

18687

AN:

53396

Middle Eastern (MID)

AF:

0.198

AC:

1142

AN:

5766

European-Non Finnish (NFE)

AF:

0.262

AC:

291167

AN:

1111750

Other (OTH)

AF:

0.256

AC:

15476

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

14965

29931

44896

59862

74827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9724

19448

29172

38896

48620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.282

AC:

42880

AN:

152126

Hom.:

6394

Cov.:

AF XY:

0.280

AC XY:

20802

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.349

AC:

14479

AN:

41508

American (AMR)

AF:

0.177

AC:

2706

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

848

AN:

3472

East Asian (EAS)

AF:

0.330

AC:

1708

AN:

5174

South Asian (SAS)

AF:

0.104

AC:

502

AN:

4818

European-Finnish (FIN)

AF:

0.349

AC:

3692

AN:

10572

Middle Eastern (MID)

AF:

0.219

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.267

AC:

18178

AN:

67984

Other (OTH)

AF:

0.256

AC:

541

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1614

3227

4841

6454

8068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.264

Hom.:

18468

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

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

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

PhyloP100

0.81

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

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over