NM_207517.3:c.728-4763C>T

Variant names:

• chr15-83854003-C-T
• rs1383484
• NM_207517.3:c.728-4763C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207517.3(ADAMTSL3):​c.728-4763C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,822 control chromosomes in the GnomAD database, including 8,853 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 0.33 (8853 hom., cov: 31)
• Consequence: ADAMTSL3 NM_207517.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3	c.728-4763C>T		intron_variant	Intron 7 of 29	ENST00000286744.10	NP_997400.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL3	ENST00000286744.10	c.728-4763C>T		intron_variant	Intron 7 of 29	1	NM_207517.3	ENSP00000286744.5
ADAMTSL3	ENST00000567476.1	c.728-4763C>T		intron_variant	Intron 7 of 29	1		ENSP00000456313.1
ADAMTSL3	ENST00000561483.5	n.943-4763C>T		intron_variant	Intron 7 of 26	5
ADAMTSL3	ENST00000569510.5	n.943-4763C>T		intron_variant	Intron 7 of 8	2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49513 AN: 151704 Hom.: 8830 Cov.: 31

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.327 AC: 49598 AN: 151822 Hom.: 8853 Cov.: 31 AF XY: 0.331 AC XY: 24570 AN XY: 74202

African (AFR) AF: 0.398 AC: 16466 AN: 41374

American (AMR) AF: 0.456 AC: 6954 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3468

East Asian (EAS) AF: 0.564 AC: 2908 AN: 5154

South Asian (SAS) AF: 0.460 AC: 2213 AN: 4806

European-Finnish (FIN) AF: 0.229 AC: 2416 AN: 10534

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16653 AN: 67930

Other (OTH) AF: 0.318 AC: 670 AN: 2104

Alfa AF: 0.279 Hom.: 18492

Bravo AF: 0.344

Asia WGS AF: 0.515 AC: 1763 AN: 3434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.24
DANN	Benign	0.50
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1383484; hg19: chr15-84522755;