Genetic Variant ADAMTSL3:c.364-132dupA (chr15-83819661-C-CA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207517.3(ADAMTSL3):c.364-132dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00643 in 522,646 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0049 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0069 ( 0 hom. )

Consequence

ADAMTSL3
NM_207517.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.436

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Variant has high frequency in the AFR (0.0115) population. However there is too low homozygotes in high coverage region: (expected more than 5, got 0).

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.364-132dupA		intron	N/A	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.364-132dupA		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.364-150_364-149insA	intron	N/A	ENSP00000286744.5	P82987-1
ADAMTSL3	ENST00000567476.1	TSL:1	c.364-150_364-149insA	intron	N/A	ENSP00000456313.1	P82987-2
ADAMTSL3	ENST00000963409.1		c.364-150_364-149insA	intron	N/A	ENSP00000633468.1

Frequencies

GnomAD3 genomes

AF:

0.00492

AC:

593

AN:

120458

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00189

Gnomad ASJ

AF:

0.00473

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000339

Gnomad MID

AF:

0.00385

Gnomad NFE

AF:

0.00105

Gnomad OTH

AF:

0.00305

GnomAD4 exome

AF:

0.00688

AC:

2766

AN:

402234

Hom.:

AF XY:

0.00677

AC XY:

1427

AN XY:

210780

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0132

AC:

150

AN:

11374

American (AMR)

AF:

0.00499

AC:

AN:

17426

Ashkenazi Jewish (ASJ)

AF:

0.0100

AC:

123

AN:

12288

East Asian (EAS)

AF:

0.000799

AC:

AN:

28786

South Asian (SAS)

AF:

0.00286

AC:

107

AN:

37420

European-Finnish (FIN)

AF:

0.00689

AC:

189

AN:

27412

Middle Eastern (MID)

AF:

0.00509

AC:

AN:

1768

European-Non Finnish (NFE)

AF:

0.00789

AC:

1914

AN:

242442

Other (OTH)

AF:

0.00703

AC:

164

AN:

23318

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.286

Heterozygous variant carriers

209

418

626

835

1044

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00492

AC:

593

AN:

120412

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

300

AN XY:

57142

show subpopulations

African (AFR)

AF:

0.0152

AC:

488

AN:

32072

American (AMR)

AF:

0.00189

AC:

AN:

12160

Ashkenazi Jewish (ASJ)

AF:

0.00473

AC:

AN:

2962

East Asian (EAS)

AF:

0.00

AC:

AN:

4230

South Asian (SAS)

AF:

0.00

AC:

AN:

3530

European-Finnish (FIN)

AF:

0.000339

AC:

AN:

5906

Middle Eastern (MID)

AF:

0.00431

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.00105

AC:

AN:

56898

Other (OTH)

AF:

0.00305

AC:

AN:

1642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.44

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

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

15-83819661-CAAAAAAA-CAAAAAAAA

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