15-83773520-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_207517.3(ADAMTSL3):c.190-3T>C variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004424
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0100

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
ADAMTSL3	NM_207517.3	c.190-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000286744.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL3	ENST00000286744.10	c.190-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_207517.3	P1

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9581 AN: 151970 Hom.: 386 Cov.: 32

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

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.: 33 AF XY: 0.0663 AC XY: 48161 AN XY: 726762

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.: 32 AF XY: 0.0645 AC XY: 4797 AN XY: 74348

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

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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

Other links and lift over

dbSNP: rs75442575; hg19: chr15-84442272; COSMIC: COSV54437728;