rs3731980
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_025000.4(DCAF17):c.1320T>C(p.Ala440=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,613,878 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0019 ( 9 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 52 hom. )
Consequence
DCAF17
NM_025000.4 synonymous
NM_025000.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0980
Genes affected
DCAF17 (HGNC:25784): (DDB1 and CUL4 associated factor 17) This gene encodes a nuclear transmembrane protein that associates with cullin 4A/damaged DNA binding protein 1 ubiquitin ligase complex. Mutations in this gene are associated with Woodhouse-Sakati syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 2-171480091-T-C is Benign according to our data. Variant chr2-171480091-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 128888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.098 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0019 (289/152344) while in subpopulation EAS AF= 0.0424 (220/5192). AF 95% confidence interval is 0.0378. There are 9 homozygotes in gnomad4. There are 156 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DCAF17 | NM_025000.4 | c.1320T>C | p.Ala440= | synonymous_variant | 13/14 | ENST00000375255.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DCAF17 | ENST00000375255.8 | c.1320T>C | p.Ala440= | synonymous_variant | 13/14 | 1 | NM_025000.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00190 AC: 289AN: 152226Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00279 AC: 701AN: 250998Hom.: 23 AF XY: 0.00257 AC XY: 348AN XY: 135646
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GnomAD4 exome AF: 0.00119 AC: 1735AN: 1461534Hom.: 52 Cov.: 31 AF XY: 0.00112 AC XY: 811AN XY: 727066
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GnomAD4 genome ? AF: 0.00190 AC: 289AN: 152344Hom.: 9 Cov.: 32 AF XY: 0.00209 AC XY: 156AN XY: 74498
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Woodhouse-Sakati syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Mutations in DCAF17 have been associated with a rare syndrome called Woodhouse Sakati Syndrome, which can have diabetes mellitus as one of the presentations.However no sufficient evidence is found to ascertain the role of this particular variant rs3731980, yet. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 09, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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