5-33596119-C-T

Variant names:

• chr5-33596119-C-T
• rs10461703
• NM_030955.4:c.2528-59G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADAMTS12	NM_030955.4	c.2528-59G>A		intron_variant	Intron 16 of 23	ENST00000504830.6	NP_112217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS12	ENST00000504830.6	c.2528-59G>A		intron_variant	Intron 16 of 23	1	NM_030955.4	ENSP00000422554.1
ADAMTS12	ENST00000352040.7	c.2273-59G>A		intron_variant	Intron 14 of 21	1		ENSP00000344847.3
ADAMTS12	ENST00000504582.5	n.2208-59G>A		intron_variant	Intron 15 of 17	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

African (AFR) AF: 0.299 AC: 9893 AN: 33128

American (AMR) AF: 0.501 AC: 21873 AN: 43634

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 14766 AN: 25238

East Asian (EAS) AF: 0.570 AC: 22536 AN: 39532

South Asian (SAS) AF: 0.610 AC: 50998 AN: 83654

European-Finnish (FIN) AF: 0.462 AC: 24073 AN: 52110

Middle Eastern (MID) AF: 0.638 AC: 2933 AN: 4596

European-Non Finnish (NFE) AF: 0.548 AC: 603695 AN: 1102392

Other (OTH) AF: 0.537 AC: 32043 AN: 59674

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

African (AFR) AF: 0.307 AC: 12732 AN: 41428

American (AMR) AF: 0.484 AC: 7391 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2062 AN: 3464

East Asian (EAS) AF: 0.571 AC: 2934 AN: 5142

South Asian (SAS) AF: 0.603 AC: 2898 AN: 4808

European-Finnish (FIN) AF: 0.458 AC: 4823 AN: 10542

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37218 AN: 67836

Other (OTH) AF: 0.499 AC: 1044 AN: 2092

Alfa AF: 0.533 Hom.: 11187

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
PhyloP100		-0.048
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: rs10461703; hg19: chr5-33596224;