Genetic Variant ADAMTSL3:c.364-34T>C (chr15-83819777-T-C) – 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.364-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,530,012 control chromosomes in the GnomAD database, including 25,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2001 hom., cov: 31)

Exomes 𝑓: 0.18 ( 23596 hom. )

Consequence

ADAMTSL3
NM_207517.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.17

Publications

8 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:

Genome browser will be placed here

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=-0.83).

BP6

Variant 15-83819777-T-C is Benign according to our data. Variant chr15-83819777-T-C is described in ClinVar as Benign. ClinVar VariationId is 1252346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 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.364-34T>C		intron	N/A	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.364-34T>C		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.364-34T>C	intron	N/A	ENSP00000286744.5	P82987-1
ADAMTSL3	ENST00000567476.1	TSL:1	c.364-34T>C	intron	N/A	ENSP00000456313.1	P82987-2
ADAMTSL3	ENST00000963409.1		c.364-34T>C	intron	N/A	ENSP00000633468.1

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21542

AN:

151866

Hom.:

2004

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0344

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.0364

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.167

GnomAD2 exomes

AF:

0.163

AC:

40829

AN:

250086

AF XY:

0.170

show subpopulations

Gnomad AFR exome

AF:

0.0298

Gnomad AMR exome

AF:

0.146

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.0343

Gnomad FIN exome

AF:

0.156

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.190

GnomAD4 exome

AF:

0.177

AC:

244594

AN:

1378038

Hom.:

23596

Cov.:

AF XY:

0.179

AC XY:

123510

AN XY:

689828

show subpopulations

African (AFR)

AF:

0.0298

AC:

940

AN:

31526

American (AMR)

AF:

0.149

AC:

6624

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

5713

AN:

25586

East Asian (EAS)

AF:

0.0321

AC:

1257

AN:

39182

South Asian (SAS)

AF:

0.173

AC:

14631

AN:

84360

European-Finnish (FIN)

AF:

0.154

AC:

8196

AN:

53304

Middle Eastern (MID)

AF:

0.357

AC:

1536

AN:

4300

European-Non Finnish (NFE)

AF:

0.189

AC:

195666

AN:

1037692

Other (OTH)

AF:

0.174

AC:

10031

AN:

57502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

9680

19360

29039

38719

48399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6324

12648

18972

25296

31620

<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:

0.142

AC:

21540

AN:

151974

Hom.:

2001

Cov.:

AF XY:

0.141

AC XY:

10461

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.0344

AC:

1426

AN:

41472

American (AMR)

AF:

0.165

AC:

2510

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

760

AN:

3468

East Asian (EAS)

AF:

0.0363

AC:

188

AN:

5174

South Asian (SAS)

AF:

0.158

AC:

760

AN:

4814

European-Finnish (FIN)

AF:

0.155

AC:

1633

AN:

10560

Middle Eastern (MID)

AF:

0.336

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.199

AC:

13543

AN:

67936

Other (OTH)

AF:

0.165

AC:

348

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

901

1802

2704

3605

4506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<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:

0.181

Hom.:

545

Bravo

AF:

0.138

Asia WGS

AF:

0.0960

AC:

333

AN:

3478

ClinVar

ClinVar submissions

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

-0.83

CADD

Benign

6.0

(source)

DANN

Benign

0.68

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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