NM_025000.4:c.939G>A

Variant names:

• chr2-171468988-G-A
• rs61731491
• NM_025000.4:c.939G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_025000.4(DCAF17):​c.939G>A​(p.Gln313Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00766 in 1,614,050 control chromosomes in the GnomAD database, including 722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (394 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (328 hom.)
• Consequence: DCAF17 NM_025000.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.324
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Woodhouse-Sakati syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.098).
• BP6: Variant 2-171468988-G-A is Benign according to our data. Variant chr2-171468988-G-A is described in ClinVar as Benign. ClinVar VariationId is 128891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.324 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025000.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF17	NM_025000.4	MANE Select	c.939G>A	p.Gln313Gln	synonymous	Exon 9 of 14	NP_079276.2	Q5H9S7-1
	DCAF17	NM_001164821.2		c.939G>A	p.Gln313Gln	synonymous	Exon 9 of 12	NP_001158293.1	F5H7W1
	DCAF17	NR_028482.2		n.1185G>A		non_coding_transcript_exon	Exon 8 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCAF17	ENST00000375255.8	TSL:1 MANE Select	c.939G>A	p.Gln313Gln	synonymous	Exon 9 of 14	ENSP00000364404.3	Q5H9S7-1
	DCAF17	ENST00000339506.7	TSL:1	c.189G>A	p.Gln63Gln	synonymous	Exon 2 of 7	ENSP00000342160.3	H0Y2X0
	DCAF17	ENST00000966668.1		c.990G>A	p.Gln330Gln	synonymous	Exon 10 of 15	ENSP00000636727.1

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 6023 AN: 152150 Hom.: 395 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.0297

GnomAD2 exomes AF: 0.0110 AC: 2769 AN: 251188 AF XY: 0.00825

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.00888

Gnomad ASJ exome AF: 0.00645

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000687

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00434 AC: 6342 AN: 1461782 Hom.: 328 Cov.: 31 AF XY: 0.00380 AC XY: 2763 AN XY: 727186

African (AFR) AF: 0.136 AC: 4543 AN: 33470

American (AMR) AF: 0.00975 AC: 436 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 173 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000441 AC: 38 AN: 86254

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.0109 AC: 63 AN: 5766

European-Non Finnish (NFE) AF: 0.000435 AC: 484 AN: 1111956

Other (OTH) AF: 0.0100 AC: 604 AN: 60392

GnomAD4 genome AF: 0.0395 AC: 6022 AN: 152268 Hom.: 394 Cov.: 32 AF XY: 0.0386 AC XY: 2875 AN XY: 74454

African (AFR) AF: 0.132 AC: 5496 AN: 41526

American (AMR) AF: 0.0242 AC: 371 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000853 AC: 58 AN: 68024

Other (OTH) AF: 0.0294 AC: 62 AN: 2112

Alfa AF: 0.0216 Hom.: 165

Bravo AF: 0.0451

Asia WGS AF: 0.00751 AC: 27 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Woodhouse-Sakati syndrome (3)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.6
DANN	Benign	0.51
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61731491; hg19: chr2-172325498; COSMIC: COSV59829555; COSMIC: COSV59829555;