Genetic Variant ADAMTSL3:c.364-135_364-132delAAAA (chr15-83819661-CAAAA-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.364-135_364-132delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 506,416 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 0.00016 ( 0 hom., cov: 0)

Exomes 𝑓: 0.018 ( 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 (0.0315) population. However there is too low homozygotes in high coverage region: (expected more than 25, 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.364-135_364-132delAAAA		intron	N/A	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.364-135_364-132delAAAA		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_364-146delAAAA	intron	N/A	ENSP00000286744.5	P82987-1
ADAMTSL3	ENST00000567476.1	TSL:1	c.364-149_364-146delAAAA	intron	N/A	ENSP00000456313.1	P82987-2
ADAMTSL3	ENST00000963409.1		c.364-149_364-146delAAAA	intron	N/A	ENSP00000633468.1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

120460

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:

0.000235

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00186

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000123

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0184

AC:

7110

AN:

385956

Hom.:

AF XY:

0.0190

AC XY:

3834

AN XY:

202172

show subpopulations

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

African (AFR)

AF:

0.0104

AC:

114

AN:

10946

American (AMR)

AF:

0.0170

AC:

282

AN:

16618

Ashkenazi Jewish (ASJ)

AF:

0.0160

AC:

190

AN:

11866

East Asian (EAS)

AF:

0.0158

AC:

429

AN:

27142

South Asian (SAS)

AF:

0.0331

AC:

1175

AN:

35486

European-Finnish (FIN)

AF:

0.0165

AC:

436

AN:

26428

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

1694

European-Non Finnish (NFE)

AF:

0.0175

AC:

4081

AN:

233350

Other (OTH)

AF:

0.0169

AC:

380

AN:

22426

⚠️ 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: 0.258

Heterozygous variant carriers

870

1740

2611

3481

4351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.000158

AC:

AN:

120460

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

AN XY:

57148

show subpopulations

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

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:

0.000235

AC:

AN:

4248

South Asian (SAS)

AF:

0.00

AC:

AN:

3552

European-Finnish (FIN)

AF:

0.00186

AC:

AN:

5900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.000123

AC:

AN:

56908

Other (OTH)

AF:

0.00

AC:

AN:

1638

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.288

Heterozygous variant carriers

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

Mutation Taster

=100/0

polymorphism

(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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15-83819661-CAAAAAAA-CAAA

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