rs4359399

Positions:

• chr15-83976300-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207517.3(ADAMTSL3):​c.2644+5663T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,696 control chromosomes in the GnomAD database, including 19,241 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19241 hom., cov: 30)
• Consequence: ADAMTSL3 NM_207517.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3	c.2644+5663T>A		intron_variant		ENST00000286744.10	NP_997400.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTSL3	ENST00000286744.10	c.2644+5663T>A		intron_variant		1	NM_207517.3	ENSP00000286744.5

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75831 AN: 151578 Hom.: 19233 Cov.: 30

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.496

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.500 AC: 75872 AN: 151696 Hom.: 19241 Cov.: 30 AF XY: 0.499 AC XY: 36965 AN XY: 74108

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.489

Alfa AF: 0.514 Hom.: 2858

Bravo AF: 0.490

Asia WGS AF: 0.357 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs4359399; hg19: chr15-84645052;