Genetic Variant ADAMTSL3:c.363+58A>G (chr15-83804753-A-G) – 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.363+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0996 in 1,331,686 control chromosomes in the GnomAD database, including 10,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2466 hom., cov: 30)

Exomes 𝑓: 0.093 ( 7722 hom. )

Consequence

ADAMTSL3
NM_207517.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.44

Publications

7 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:

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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=-0.85).

BP6

Variant 15-83804753-A-G is Benign according to our data. Variant chr15-83804753-A-G is described in ClinVar as Benign. ClinVar VariationId is 1257800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207517.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL3	NM_207517.3	MANE Select	c.363+58A>G		intron	N/A	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.363+58A>G		intron	N/A	NP_001288039.1	P82987-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADAMTSL3	ENST00000286744.10	TSL:1 MANE Select	c.363+58A>G	intron	N/A	ENSP00000286744.5	P82987-1
ADAMTSL3	ENST00000567476.1	TSL:1	c.363+58A>G	intron	N/A	ENSP00000456313.1	P82987-2
ADAMTSL3	ENST00000963409.1		c.363+58A>G	intron	N/A	ENSP00000633468.1

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22659

AN:

151984

Hom.:

2459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.0904

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0683

Gnomad OTH

AF:

0.145

GnomAD4 exome

AF:

0.0932

AC:

109941

AN:

1179584

Hom.:

7722

AF XY:

0.0972

AC XY:

57362

AN XY:

590296

show subpopulations

African (AFR)

AF:

0.287

AC:

7250

AN:

25260

American (AMR)

AF:

0.0863

AC:

2045

AN:

23686

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

3464

AN:

22372

East Asian (EAS)

AF:

0.252

AC:

8783

AN:

34878

South Asian (SAS)

AF:

0.264

AC:

17121

AN:

64762

European-Finnish (FIN)

AF:

0.0921

AC:

4609

AN:

50036

Middle Eastern (MID)

AF:

0.123

AC:

603

AN:

4900

European-Non Finnish (NFE)

AF:

0.0664

AC:

60050

AN:

903776

Other (OTH)

AF:

0.121

AC:

6016

AN:

49914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

4567

9133

13700

18266

22833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2450

4900

7350

9800

12250

<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:

0.149

AC:

22694

AN:

152102

Hom.:

2466

Cov.:

AF XY:

0.153

AC XY:

11353

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.284

AC:

11789

AN:

41448

American (AMR)

AF:

0.101

AC:

1545

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

566

AN:

3470

East Asian (EAS)

AF:

0.277

AC:

1436

AN:

5178

South Asian (SAS)

AF:

0.290

AC:

1397

AN:

4810

European-Finnish (FIN)

AF:

0.0904

AC:

958

AN:

10594

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0683

AC:

4646

AN:

68016

Other (OTH)

AF:

0.144

AC:

304

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

903

1806

2708

3611

4514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.136

Hom.:

272

Bravo

AF:

0.153

Asia WGS

AF:

0.292

AC:

1011

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.4

(source)

DANN

Benign

0.61

PhyloP100

1.4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over