20-64048274-C-T
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_018419.3(SOX18):c.1047G>A(p.Leu349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000702 in 1,596,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000075 ( 0 hom. )
Consequence
SOX18
NM_018419.3 synonymous
NM_018419.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.32
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 Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 20-64048274-C-T is Benign according to our data. Variant chr20-64048274-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1922877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.32 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000755 (109/1444298) while in subpopulation NFE AF= 0.0000914 (101/1104774). AF 95% confidence interval is 0.0000765. There are 0 homozygotes in gnomad4_exome. There are 51 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX18 | NM_018419.3 | c.1047G>A | p.Leu349= | synonymous_variant | 2/2 | ENST00000340356.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX18 | ENST00000340356.9 | c.1047G>A | p.Leu349= | synonymous_variant | 2/2 | 1 | NM_018419.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000939 AC: 2AN: 212890Hom.: 0 AF XY: 0.0000172 AC XY: 2AN XY: 116412
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GnomAD4 exome AF: 0.0000755 AC: 109AN: 1444298Hom.: 0 Cov.: 31 AF XY: 0.0000711 AC XY: 51AN XY: 716942
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74338
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
SOX18-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 11, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 29, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at