rs587777695
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM2PP2PP3_ModeratePP5_Very_Strong
The NM_020928.2(ZSWIM6):c.3487C>T(p.Arg1163Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1163Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_020928.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZSWIM6 | NM_020928.2 | c.3487C>T | p.Arg1163Trp | missense_variant | 14/14 | ENST00000252744.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZSWIM6 | ENST00000252744.6 | c.3487C>T | p.Arg1163Trp | missense_variant | 14/14 | 5 | NM_020928.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Cov.: 33
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Acromelic frontonasal dysostosis Pathogenic:5Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Daryl Scott Lab, Baylor College of Medicine | Nov 10, 2023 | - - |
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpretted as pathogenic and reported on 09/20/2018 by GTR ID 239772. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Likely pathogenic, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | May 31, 2018 | This variant is interpreted as a Likely Pathogenic, for Acromelic frontonasal dysostosis, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: PM6 => Assumed de novo, but without confirmation of paternity and maternity (PMID:25105228). PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => Observed in multiple unrelated patients. (PMID:25105228,26706854). - |
Pathogenic, criteria provided, single submitter | research | University of Washington Center for Mendelian Genomics, University of Washington | Sep 23, 2014 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 07, 2014 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Oct 11, 2017 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | ZSWIM6: PS2:Very Strong, PM2, PP2, PS3:Supporting - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 13, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25105228, 33776626, 26706854) - |
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 02, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at