chr9-133422463-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_139027.6(ADAMTS13):c.20G>A(p.Arg7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7W) has been classified as Likely benign.
Frequency
Consequence
NM_139027.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAMTS13 | NM_139027.6 | c.20G>A | p.Arg7Gln | missense_variant | 1/29 | ENST00000355699.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAMTS13 | ENST00000355699.7 | c.20G>A | p.Arg7Gln | missense_variant | 1/29 | 1 | NM_139027.6 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251126Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135782
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461610Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727140
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74312
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 25, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 7 of the ADAMTS13 protein (p.Arg7Gln). This variant is present in population databases (rs782744929, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ADAMTS13-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at