Genetic Variant ADAMTSL3:c.364-136_364-132delAAAAA (chr15-83819661-CAAAAA-C) – 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.364-136_364-132delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 518,918 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 0.000025 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0037 ( 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 SAS (0.00637) population. However there is too low homozygotes in high coverage region: (expected more than 1, 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.364-136_364-132delAAAAA		intron	N/A	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.364-136_364-132delAAAAA		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.364-149_364-145delAAAAA	intron	N/A	ENSP00000286744.5	P82987-1
ADAMTSL3	ENST00000567476.1	TSL:1	c.364-149_364-145delAAAAA	intron	N/A	ENSP00000456313.1	P82987-2
ADAMTSL3	ENST00000963409.1		c.364-149_364-145delAAAAA	intron	N/A	ENSP00000633468.1

Frequencies

GnomAD3 genomes

AF:

0.0000249

AC:

AN:

120474

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000351

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00365

AC:

1455

AN:

398444

Hom.:

AF XY:

0.00379

AC XY:

792

AN XY:

208766

show subpopulations

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

African (AFR)

AF:

0.00150

AC:

AN:

11306

American (AMR)

AF:

0.00324

AC:

AN:

17268

Ashkenazi Jewish (ASJ)

AF:

0.00255

AC:

AN:

12178

East Asian (EAS)

AF:

0.00271

AC:

AN:

28372

South Asian (SAS)

AF:

0.00707

AC:

261

AN:

36896

European-Finnish (FIN)

AF:

0.00327

AC:

AN:

27226

Middle Eastern (MID)

AF:

0.00287

AC:

AN:

1742

European-Non Finnish (NFE)

AF:

0.00354

AC:

852

AN:

240352

Other (OTH)

AF:

0.00290

AC:

AN:

23104

⚠️ 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: 0.251

Heterozygous variant carriers

200

399

599

798

998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000249

AC:

AN:

120474

Hom.:

Cov.:

AF XY:

0.0000525

AC XY:

AN XY:

57152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32054

American (AMR)

AF:

0.00

AC:

AN:

12158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2962

East Asian (EAS)

AF:

0.00

AC:

AN:

4248

South Asian (SAS)

AF:

0.00

AC:

AN:

3552

European-Finnish (FIN)

AF:

0.000169

AC:

AN:

5902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.0000351

AC:

AN:

56920

Other (OTH)

AF:

0.00

AC:

AN:

1638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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15-83819661-CAAAAAAA-CAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over