5-33530424-C-T

Variant names:

• chr5-33530424-C-T
• rs256603
• NM_030955.4:c.4607-3058G>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.4607-3058G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,124 control chromosomes in the GnomAD database, including 18,779 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 0.48 (18779 hom., cov: 33)
• Consequence: ADAMTS12 NM_030955.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030955.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS12	NM_030955.4	MANE Select	c.4607-3058G>A		intron	N/A	NP_112217.2	P58397-1
	ADAMTS12	NM_001324512.2		c.4352-3058G>A		intron	N/A	NP_001311441.1	P58397-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS12	ENST00000504830.6	TSL:1 MANE Select	c.4607-3058G>A		intron	N/A	ENSP00000422554.1	P58397-1
	ADAMTS12	ENST00000352040.7	TSL:1	c.4352-3058G>A		intron	N/A	ENSP00000344847.3	P58397-3

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73117 AN: 152006 Hom.: 18746 Cov.: 33

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.481 AC: 73201 AN: 152124 Hom.: 18779 Cov.: 33 AF XY: 0.487 AC XY: 36221 AN XY: 74374

African (AFR) AF: 0.607 AC: 25202 AN: 41494

American (AMR) AF: 0.497 AC: 7604 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1108 AN: 3470

East Asian (EAS) AF: 0.775 AC: 4001 AN: 5162

South Asian (SAS) AF: 0.645 AC: 3111 AN: 4822

European-Finnish (FIN) AF: 0.385 AC: 4073 AN: 10588

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26575 AN: 67972

Other (OTH) AF: 0.469 AC: 992 AN: 2114

Alfa AF: 0.442 Hom.: 1996

Bravo AF: 0.498

Asia WGS AF: 0.683 AC: 2376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.52
PhyloP100		-0.092
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: rs256603; hg19: chr5-33530529;