5-33596119-C-T

Position:

• chr5-33596119-C-T

Variant summary

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

The NM_030955.4(ADAMTS12):​c.2528-59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,595,736 control chromosomes in the GnomAD database, including 231,615 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 0.47 (17770 hom., cov: 32)
  • Exomes 𝑓: 0.54 (213845 hom.)
• Consequence: ADAMTS12 NM_030955.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

Genes affected

ADAMTS12 (HGNC:14605): (ADAM metallopeptidase with thrombospondin type 1 motif 12) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS-1) motif. Individual members of this family differ in the number of C-terminal TS-1 motifs, and some have unique C-terminal domains. The enzyme encoded by this gene contains eight TS-1 motifs. It may play roles in pulmonary cells during fetal development or in tumor processes through its proteolytic activity or as a molecule potentially involved in regulation of cell adhesion. [provided by RefSeq, Jul 2008]

ADAMTS12 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS12	NM_030955.4	c.2528-59G>A		intron_variant		ENST00000504830.6	NP_112217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS12	ENST00000504830.6	c.2528-59G>A		intron_variant		1	NM_030955.4	ENSP00000422554.1
ADAMTS12	ENST00000352040.7	c.2273-59G>A		intron_variant		1		ENSP00000344847.3
ADAMTS12	ENST00000504582.5	n.2208-59G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71709 AN: 151662 Hom.: 17766 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.542 AC: 782810 AN: 1443958 Hom.: 213845 AF XY: 0.545 AC XY: 391216 AN XY: 717318

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.501

Gnomad4 ASJ exome AF: 0.585

Gnomad4 EAS exome AF: 0.570

Gnomad4 SAS exome AF: 0.610

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.548

Gnomad4 OTH exome AF: 0.537

GnomAD4 genome AF: 0.473 AC: 71729 AN: 151778 Hom.: 17770 Cov.: 32 AF XY: 0.471 AC XY: 34914 AN XY: 74188

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.499

Alfa AF: 0.534 Hom.: 10019

Bravo AF: 0.470

Asia WGS AF: 0.552 AC: 1917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.5
DANN	Benign	0.87

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: rs10461703; hg19: chr5-33596224;