Genetic Variant ADAMTSL3:c.1468-66C>T (chr15-83897792-C-T) – 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.1468-66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,490,046 control chromosomes in the GnomAD database, including 47,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6075 hom., cov: 32)

Exomes 𝑓: 0.24 ( 41456 hom. )

Consequence

ADAMTSL3
NM_207517.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.106

Publications

11 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=-0.97).

BP6

Variant 15-83897792-C-T is Benign according to our data. Variant chr15-83897792-C-T is described in ClinVar as Benign. ClinVar VariationId is 1265153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 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.1468-66C>T		intron	N/A	NP_997400.2
	ADAMTSL3	NM_001301110.2		c.1468-66C>T		intron	N/A	NP_001288039.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADAMTSL3	ENST00000286744.10	TSL:1 MANE Select	c.1468-66C>T	intron	N/A	ENSP00000286744.5
ADAMTSL3	ENST00000567476.1	TSL:1	c.1468-66C>T	intron	N/A	ENSP00000456313.1
ADAMTSL3	ENST00000963409.1		c.1468-66C>T	intron	N/A	ENSP00000633468.1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40995

AN:

151942

Hom.:

6051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.360

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.268

GnomAD4 exome

AF:

0.239

AC:

319300

AN:

1337986

Hom.:

41456

AF XY:

0.240

AC XY:

157531

AN XY:

656522

show subpopulations

African (AFR)

AF:

0.304

AC:

9138

AN:

30014

American (AMR)

AF:

0.539

AC:

16278

AN:

30206

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

5683

AN:

20646

East Asian (EAS)

AF:

0.360

AC:

13793

AN:

38282

South Asian (SAS)

AF:

0.371

AC:

24361

AN:

65696

European-Finnish (FIN)

AF:

0.203

AC:

9922

AN:

48816

Middle Eastern (MID)

AF:

0.183

AC:

965

AN:

5286

European-Non Finnish (NFE)

AF:

0.216

AC:

225425

AN:

1044064

Other (OTH)

AF:

0.250

AC:

13735

AN:

54976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

11403

22807

34210

45614

57017

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8582

17164

25746

34328

42910

<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:

0.270

AC:

41072

AN:

152060

Hom.:

6075

Cov.:

AF XY:

0.274

AC XY:

20372

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.308

AC:

12762

AN:

41486

American (AMR)

AF:

0.432

AC:

6602

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

1006

AN:

3472

East Asian (EAS)

AF:

0.361

AC:

1864

AN:

5170

South Asian (SAS)

AF:

0.392

AC:

1889

AN:

4816

European-Finnish (FIN)

AF:

0.202

AC:

2134

AN:

10550

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14062

AN:

67976

Other (OTH)

AF:

0.270

AC:

568

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1532

3064

4597

6129

7661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.231

Hom.:

2301

Bravo

AF:

0.287

Asia WGS

AF:

0.390

AC:

1354

AN:

3478

ClinVar

ClinVar submissions as Germline

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

-0.97

CADD

Benign

5.8

(source)

DANN

Benign

0.48

PhyloP100

0.11

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