9-17938353-T-C

Position:

• chr9-17938353-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000680146.1(ADAMTSL1):​c.87+31431T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,882 control chromosomes in the GnomAD database, including 23,451 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 0.54 (23451 hom., cov: 31)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909

Genes affected

ADAMTSL1 (HGNC:14632): (ADAMTS like 1) This gene encodes a secreted protein and member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) family. This protein lacks the metalloproteinase and disintegrin-like domains, which are typical of the ADAMTS family, but contains other ADAMTS domains, including the thrombospondin type 1 motif. This protein may have important functions in the extracellular matrix. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL1	XM_011518063.3	c.141+5328T>C		intron_variant
ADAMTSL1	XM_011518064.4	c.96+31431T>C		intron_variant
ADAMTSL1	XM_017015311.2	c.141+5328T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.87+31431T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81870 AN: 151764 Hom.: 23445 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.539 AC: 81888 AN: 151882 Hom.: 23451 Cov.: 31 AF XY: 0.543 AC XY: 40280 AN XY: 74176

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.558

Alfa AF: 0.600 Hom.: 62314

Bravo AF: 0.526

Asia WGS AF: 0.537 AC: 1867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1755289; hg19: chr9-17938351;