rs121908476

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000355699.7(ADAMTS13):ā€‹c.1345C>Gā€‹(p.Gln449Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,435,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

ADAMTS13
ENST00000355699.7 missense

Scores

7
9
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.29
Variant links:
Genes affected
ADAMTS13 (HGNC:1366): (ADAM metallopeptidase with thrombospondin type 1 motif 13) This gene encodes a member of a family of proteins containing several distinct regions, including a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. The enzyme encoded by this gene specifically cleaves von Willebrand Factor (vWF). Defects in this gene are associated with thrombotic thrombocytopenic purpura. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.913

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADAMTS13NM_139027.6 linkuse as main transcriptc.1345C>G p.Gln449Glu missense_variant 12/29 ENST00000355699.7 NP_620596.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADAMTS13ENST00000355699.7 linkuse as main transcriptc.1345C>G p.Gln449Glu missense_variant 12/291 NM_139027.6 ENSP00000347927 A2Q76LX8-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000486
AC:
1
AN:
205952
Hom.:
0
AF XY:
0.00000898
AC XY:
1
AN XY:
111298
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000381
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.96e-7
AC:
1
AN:
1435866
Hom.:
0
Cov.:
35
AF XY:
0.00000140
AC XY:
1
AN XY:
711752
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000121
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Pathogenic
0.18
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.75
D;T;.;.
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.85
D;D;D;T
M_CAP
Uncertain
0.23
D
MetaRNN
Pathogenic
0.91
D;D;D;D
MetaSVM
Uncertain
0.66
D
MutationAssessor
Pathogenic
3.7
H;.;H;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-3.0
D;.;D;D
REVEL
Uncertain
0.41
Sift
Pathogenic
0.0
D;.;D;D
Sift4G
Uncertain
0.0050
D;D;D;.
Polyphen
1.0
D;.;D;D
Vest4
0.73
MutPred
0.67
Gain of relative solvent accessibility (P = 0.1571);.;Gain of relative solvent accessibility (P = 0.1571);.;
MVP
0.92
MPC
1.1
ClinPred
0.93
D
GERP RS
5.2
Varity_R
0.29
gMVP
0.95

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.

Other links and lift over

dbSNP: rs121908476; hg19: chr9-136301985; API