Variant rs192861143 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_025000.4(DCAF17):c.322-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,323,918 control chromosomes in the GnomAD database, including 30,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.21 ( 3118 hom., cov: 31)

Exomes 𝑓: 0.23 ( 27669 hom. )

Consequence

DCAF17
NM_025000.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:11

Conservation

PhyloP100: -0.977

Variant links:

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]

DCAF17 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-171448667-C-T is Benign according to our data. Variant chr2-171448667-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 191260.We mark this variant Likely_benign, oryginal submissions are: {Benign=6, Uncertain_significance=1}. Variant chr2-171448667-C-T is described in Lovd as [Benign]. Variant chr2-171448667-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF17	NM_025000.4 linkuse as main transcript	c.322-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000375255.8	NP_079276.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF17	ENST00000375255.8 linkuse as main transcript	c.322-14C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_025000.4	ENSP00000364404	P1	Q5H9S7-1

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

29987

AN:

146066

Hom.:

3113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.221

GnomAD3 exomes

AF:

0.316

AC:

41589

AN:

131666

Hom.:

4823

AF XY:

0.321

AC XY:

22999

AN XY:

71588

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.435

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.259

Gnomad SAS exome

AF:

0.386

Gnomad FIN exome

AF:

0.312

Gnomad NFE exome

AF:

0.288

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.230

AC:

270501

AN:

1177798

Hom.:

27669

Cov.:

AF XY:

0.231

AC XY:

134832

AN XY:

583216

show subpopulations

Gnomad4 AFR exome

AF:

0.186

Gnomad4 AMR exome

AF:

0.347

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.262

Gnomad4 SAS exome

AF:

0.300

Gnomad4 FIN exome

AF:

0.222

Gnomad4 NFE exome

AF:

0.220

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.205

AC:

30011

AN:

146120

Hom.:

3118

Cov.:

AF XY:

0.207

AC XY:

14717

AN XY:

70936

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.273

Gnomad4 ASJ

AF:

0.259

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.289

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.225

Alfa

AF:

0.0996

Hom.:

142

Bravo

AF:

0.201

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:11

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Woodhouse-Sakati syndrome

Uncertain:1Benign:6

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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	clinical testing	Molecular Genetics, Royal Melbourne Hospital	Oct 04, 2021	Population allele frequency is 30% (rs192861143, 46,946/157,936 alleles, 5344 homozygotes in gnomAD v2.1). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria met: BA1 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
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 rs192861143, yet. -
Uncertain significance, criteria provided, single submitter	research	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	May 10, 2024	Found homozygous in an unaffected individual -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.31

DANN

Benign

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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