chr20-64048366-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting
The NM_018419.3(SOX18):c.955T>C(p.Trp319Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000544 in 1,580,826 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000052 ( 0 hom. )
Consequence
SOX18
NM_018419.3 missense
NM_018419.3 missense
Scores
5
12
2
Clinical Significance
Conservation
PhyloP100: 2.07
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_benign. Variant got -1 ACMG points.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000723 (11/152046) while in subpopulation AMR AF= 0.000523 (8/15290). AF 95% confidence interval is 0.00026. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX18 | NM_018419.3 | c.955T>C | p.Trp319Arg | missense_variant | 2/2 | ENST00000340356.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX18 | ENST00000340356.9 | c.955T>C | p.Trp319Arg | missense_variant | 2/2 | 1 | NM_018419.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000724 AC: 11AN: 151932Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000746 AC: 14AN: 187662Hom.: 0 AF XY: 0.0000387 AC XY: 4AN XY: 103286
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GnomAD4 exome AF: 0.0000525 AC: 75AN: 1428780Hom.: 0 Cov.: 31 AF XY: 0.0000536 AC XY: 38AN XY: 708458
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152046Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74330
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 06, 2022 | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 319 of the SOX18 protein (p.Trp319Arg). This variant is present in population databases (rs775039437, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SOX18-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.0058);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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