Genetic Variant ADAMTSL3:c.190-3T>C (chr15-83773520-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_207517.3(ADAMTSL3):c.190-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 1,612,916 control chromosomes in the GnomAD database, including 4,178 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 389 hom., cov: 32)

Exomes 𝑓: 0.066 ( 3789 hom. )

Consequence

ADAMTSL3
NM_207517.3 splice_region, intron

Scores

Splicing: ADA: 0.00004424

Clinical Significance

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

Conservation

PhyloP100: -0.0100

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 15-83773520-T-C is Benign according to our data. Variant chr15-83773520-T-C is described in ClinVar as [Benign]. Clinvar id is 1294088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3 link	c.190-3T>C		splice_region_variant, intron_variant	Intron 3 of 29	ENST00000286744.10	NP_997400.2	P82987-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL3	ENST00000286744.10 link	c.190-3T>C		splice_region_variant, intron_variant	Intron 3 of 29	1	NM_207517.3	ENSP00000286744.5		P82987-1

Frequencies

GnomAD3 genomes

AF:

0.0630

AC:

9581

AN:

151970

Hom.:

386

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0311

Gnomad ASJ

AF:

0.0465

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.0799

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0640

Gnomad OTH

AF:

0.0507

GnomAD3 exomes

AF:

0.0698

AC:

17508

AN:

250854

Hom.:

803

AF XY:

0.0707

AC XY:

9583

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.0474

Gnomad AMR exome

AF:

0.0226

Gnomad ASJ exome

AF:

0.0426

Gnomad EAS exome

AF:

0.173

Gnomad SAS exome

AF:

0.0779

Gnomad FIN exome

AF:

0.109

Gnomad NFE exome

AF:

0.0638

Gnomad OTH exome

AF:

0.0616

GnomAD4 exome

AF:

0.0661

AC:

96529

AN:

1460826

Hom.:

3789

Cov.:

AF XY:

0.0663

AC XY:

48161

AN XY:

726762

show subpopulations

Gnomad4 AFR exome

AF:

0.0474

Gnomad4 AMR exome

AF:

0.0230

Gnomad4 ASJ exome

AF:

0.0451

Gnomad4 EAS exome

AF:

0.194

Gnomad4 SAS exome

AF:

0.0763

Gnomad4 FIN exome

AF:

0.111

Gnomad4 NFE exome

AF:

0.0615

Gnomad4 OTH exome

AF:

0.0655

GnomAD4 genome

AF:

0.0631

AC:

9591

AN:

152090

Hom.:

389

Cov.:

AF XY:

0.0645

AC XY:

4797

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0469

Gnomad4 AMR

AF:

0.0310

Gnomad4 ASJ

AF:

0.0465

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.0806

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.0640

Gnomad4 OTH

AF:

0.0535

Alfa

AF:

0.0590

Hom.:

139

Bravo

AF:

0.0564

Asia WGS

AF:

0.118

AC:

412

AN:

3478

EpiCase

AF:

0.0568

EpiControl

AF:

0.0570

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.5

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000044

dbscSNV1_RF

Benign

0.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over