chr20-64048840-G-A
Variant summary
Our verdict is Pathogenic. The variant received 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_018419.3(SOX18):c.481C>T(p.Gln161*) variant causes a stop gained change involving the alteration of a non-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 (★★).
Frequency
Consequence
NM_018419.3 stop_gained
Scores
Clinical Significance
Conservation
Publications
- hypotrichosis-lymphedema-telangiectasia-renal defect syndromeInheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
- hypotrichosis-lymphedema-telangiectasia syndromeInheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
- hypotrichosis-lymphedema-telangiectasia syndrome (grouping)Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1428198Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 710636
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hypotrichosis-lymphedema-telangiectasia syndrome Pathogenic:2
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not provided Pathogenic:1
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on SOX18 function (PMID: 31358114). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 162093). This premature translational stop signal has been observed in individual(s) with SOX18-related conditions (PMID: 26148450). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln161*) in the SOX18 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 224 amino acid(s) of the SOX18 protein. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at