dbSNP rs61387269: ADAMTSL3:c.601-84C>A (chr15-83838005-C-A) – 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.601-84C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,518,212 control chromosomes in the GnomAD database, including 11,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1014 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10917 hom. )

Consequence

ADAMTSL3
NM_207517.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.107

Publications

1 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 (BayesDel_noAF=-0.77).

BP6

Variant 15-83838005-C-A is Benign according to our data. Variant chr15-83838005-C-A is described in ClinVar as Benign. ClinVar VariationId is 1252455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3 link	c.601-84C>A		intron_variant	Intron 6 of 29	ENST00000286744.10	NP_997400.2	P82987-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADAMTSL3	ENST00000286744.10 link	c.601-84C>A	intron_variant	Intron 6 of 29	1	NM_207517.3	ENSP00000286744.5	P82987-1
ADAMTSL3	ENST00000567476.1 link	c.601-84C>A	intron_variant	Intron 6 of 29	1		ENSP00000456313.1	P82987-2
ADAMTSL3	ENST00000561483.5 link	n.816-84C>A	intron_variant	Intron 6 of 26	5
ADAMTSL3	ENST00000569510.5 link	n.816-84C>A	intron_variant	Intron 6 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15562

AN:

151952

Hom.:

1015

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.0696

Gnomad ASJ

AF:

0.0867

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.0974

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.106

GnomAD4 exome

AF:

0.119

AC:

162795

AN:

1366142

Hom.:

10917

AF XY:

0.119

AC XY:

80222

AN XY:

676772

show subpopulations

African (AFR)

AF:

0.0427

AC:

1261

AN:

29538

American (AMR)

AF:

0.0564

AC:

1593

AN:

28232

Ashkenazi Jewish (ASJ)

AF:

0.0825

AC:

1867

AN:

22636

East Asian (EAS)

AF:

0.322

AC:

12260

AN:

38054

South Asian (SAS)

AF:

0.0927

AC:

6718

AN:

72472

European-Finnish (FIN)

AF:

0.156

AC:

7759

AN:

49706

Middle Eastern (MID)

AF:

0.0744

AC:

325

AN:

4368

European-Non Finnish (NFE)

AF:

0.117

AC:

124316

AN:

1064714

Other (OTH)

AF:

0.119

AC:

6696

AN:

56422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

6789

13577

20366

27154

33943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4706

9412

14118

18824

23530

<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:

0.102

AC:

15554

AN:

152070

Hom.:

1014

Cov.:

AF XY:

0.105

AC XY:

7781

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0470

AC:

1949

AN:

41510

American (AMR)

AF:

0.0694

AC:

1061

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0867

AC:

301

AN:

3472

East Asian (EAS)

AF:

0.335

AC:

1724

AN:

5140

South Asian (SAS)

AF:

0.0967

AC:

465

AN:

4810

European-Finnish (FIN)

AF:

0.164

AC:

1732

AN:

10568

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7946

AN:

67970

Other (OTH)

AF:

0.105

AC:

221

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

687

1374

2062

2749

3436

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.104

Hom.:

109

Bravo

AF:

0.0936

Asia WGS

AF:

0.160

AC:

557

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.1

(source)

DANN

Benign

0.33

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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