Genetic Variant ADAMTSL3:c.189+59_189+60insAG (chr15-83704567-C-CAG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_207517.3(ADAMTSL3):c.189+59_189+60insAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,602,662 control chromosomes in the GnomAD database, including 518,900 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.84 ( 54155 hom., cov: 0)

Exomes 𝑓: 0.80 ( 464745 hom. )

Consequence

ADAMTSL3
NM_207517.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.315

Publications

2 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 -10 ACMG points.

BP6

Variant 15-83704567-C-CAG is Benign according to our data. Variant chr15-83704567-C-CAG is described in ClinVar as Benign. ClinVar VariationId is 1221815.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 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.189+59_189+60insAG		intron	N/A	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.189+59_189+60insAG		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.189+59_189+60insAG	intron	N/A	ENSP00000286744.5	P82987-1
ADAMTSL3	ENST00000567476.1	TSL:1	c.189+59_189+60insAG	intron	N/A	ENSP00000456313.1	P82987-2
ADAMTSL3	ENST00000963409.1		c.189+59_189+60insAG	intron	N/A	ENSP00000633468.1

Frequencies

GnomAD3 genomes

AF:

0.840

AC:

127636

AN:

151868

Hom.:

54112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.935

Gnomad AMI

AF:

0.840

Gnomad AMR

AF:

0.851

Gnomad ASJ

AF:

0.865

Gnomad EAS

AF:

0.962

Gnomad SAS

AF:

0.939

Gnomad FIN

AF:

0.748

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.777

Gnomad OTH

AF:

0.837

GnomAD4 exome

AF:

0.798

AC:

1158061

AN:

1450676

Hom.:

464745

AF XY:

0.801

AC XY:

577670

AN XY:

721142

show subpopulations

African (AFR)

AF:

0.942

AC:

31023

AN:

32948

American (AMR)

AF:

0.870

AC:

37730

AN:

43378

Ashkenazi Jewish (ASJ)

AF:

0.850

AC:

21790

AN:

25644

East Asian (EAS)

AF:

0.959

AC:

37940

AN:

39582

South Asian (SAS)

AF:

0.931

AC:

78982

AN:

84874

European-Finnish (FIN)

AF:

0.752

AC:

40038

AN:

53276

Middle Eastern (MID)

AF:

0.848

AC:

4835

AN:

5702

European-Non Finnish (NFE)

AF:

0.775

AC:

857095

AN:

1105422

Other (OTH)

AF:

0.812

AC:

48628

AN:

59850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

12010

24020

36031

48041

60051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20552

41104

61656

82208

102760

<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:

0.840

AC:

127736

AN:

151986

Hom.:

54155

Cov.:

AF XY:

0.843

AC XY:

62616

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.935

AC:

38802

AN:

41500

American (AMR)

AF:

0.851

AC:

13012

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.865

AC:

3003

AN:

3470

East Asian (EAS)

AF:

0.961

AC:

4974

AN:

5174

South Asian (SAS)

AF:

0.939

AC:

4522

AN:

4816

European-Finnish (FIN)

AF:

0.748

AC:

7865

AN:

10520

Middle Eastern (MID)

AF:

0.854

AC:

251

AN:

294

European-Non Finnish (NFE)

AF:

0.777

AC:

52782

AN:

67912

Other (OTH)

AF:

0.836

AC:

1762

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1006

2013

3019

4026

5032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<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:

0.801

Hom.:

6015

Bravo

AF:

0.846

Asia WGS

AF:

0.931

AC:

3238

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.32

Mutation Taster

=19/81

disease causing

(source)

Splicing

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