rs1210062863
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_018419.3(SOX18):c.712G>T(p.Glu238Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000909 in 1,100,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 9.1e-7 ( 0 hom. )
Consequence
SOX18
NM_018419.3 stop_gained
NM_018419.3 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 6.69
Genes affected
SOX18 (HGNC:11194): (SRY-box transcription factor 18) This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. This protein plays a role in hair, blood vessel, and lymphatic vessel development. Mutations in this gene have been associated with recessive and dominant forms of hypotrichosis-lymphedema-telangiectasia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.384 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 20-64048609-C-A is Pathogenic according to our data. Variant chr20-64048609-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 433539.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX18 | NM_018419.3 | c.712G>T | p.Glu238Ter | stop_gained | 2/2 | ENST00000340356.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX18 | ENST00000340356.9 | c.712G>T | p.Glu238Ter | stop_gained | 2/2 | 1 | NM_018419.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 9.09e-7 AC: 1AN: 1100096Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 522302
GnomAD4 exome
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1
AN:
1100096
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31
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0
AN XY:
522302
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Area of Clinical and Molecular Genetics, Hospital Universitario Vall de Hebron | Aug 22, 2017 | This variant results in the creation of a termination codon instead of a glutamic acid at position 238 of the protein. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D
Vest4
GERP RS
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at