Variant 5-33549330-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030955.4(ADAMTS12):c.4179C>G(p.Asp1393Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,614,116 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00078 ( 20 hom. )

Consequence

ADAMTS12
NM_030955.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.24

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073042214).

BP6

Variant 5-33549330-G-C is Benign according to our data. Variant chr5-33549330-G-C is described in ClinVar as [Benign]. Clinvar id is 780955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.007 (1066/152240) while in subpopulation AFR AF= 0.0243 (1009/41542). AF 95% confidence interval is 0.023. There are 10 homozygotes in gnomad4. There are 486 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS12	NM_030955.4 linkuse as main transcript	c.4179C>G	p.Asp1393Glu	missense_variant	21/24	ENST00000504830.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS12	ENST00000504830.6 linkuse as main transcript	c.4179C>G	p.Asp1393Glu	missense_variant	21/24	1	NM_030955.4	P1	P58397-1
ADAMTS12	ENST00000352040.7 linkuse as main transcript	c.3924C>G	p.Asp1308Glu	missense_variant	19/22	1			P58397-3

Frequencies

GnomAD3 genomes

AF:

0.00701

AC:

1066

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00196

AC:

494

AN:

251404

Hom.:

AF XY:

0.00139

AC XY:

189

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000781

AC:

1142

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000661

AC XY:

481

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0279

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

AF:

0.00700

AC:

1066

AN:

152240

Hom.:

Cov.:

AF XY:

0.00653

AC XY:

486

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0243

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00102

Hom.:

Bravo

AF:

0.00762

ESP6500AA

AF:

0.0243

AC:

107

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00229

AC:

278

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

0.028

Eigen_PC

Benign

0.055

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0073

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

0.95

N;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.6

D;D

REVEL

Benign

0.16

Sift

Benign

0.059

T;T

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.77

P;B

Vest4

0.57

MutPred

0.20

Gain of disorder (P = 0.1503);.;

MVP

0.69

MPC

0.54

ClinPred

0.047

GERP RS

1.9

Varity_R

0.30

gMVP

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over