Genetic Variant DCAF13:p.Ser120Ser (chr8-103415350-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000297579.9(DCAF13):c.360T>C(p.Ser120Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,613,590 control chromosomes in the GnomAD database, including 42,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4005 hom., cov: 32)

Exomes 𝑓: 0.23 ( 38228 hom. )

Consequence

DCAF13
ENST00000297579.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.148

Publications

16 publications found

Variant links:

Genes affected

DCAF13 (HGNC:24535): (DDB1 and CUL4 associated factor 13) Enables estrogen receptor binding activity. Predicted to be involved in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Located in several cellular components, including centrosome; cytosol; and nuclear lumen. Part of Cul4-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

DCAF13 links:

ENSG00000285982 (HGNC:):

ENSG00000285982 links:

SLC25A32 (HGNC:29683): (solute carrier family 25 member 32) This gene encodes a member of the P(I/L)W subfamily of mitochondrial carrier family transport proteins. The encoded protein transports folate across the inner mitochondrial membrane. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2013]

SLC25A32 Gene-Disease associations (from GenCC):

exercise intolerance, riboflavin-responsive
Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

SLC25A32 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 8-103415350-T-C is Benign according to our data. Variant chr8-103415350-T-C is described in ClinVar as Benign. ClinVar VariationId is 1252673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.148 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000297579.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DCAF13	NM_015420.7	MANE Select	c.-97T>C	upstream_gene	N/A	NP_056235.5
SLC25A32	NM_030780.5	MANE Select	c.-413A>G	upstream_gene	N/A	NP_110407.2
DCAF13	NM_001416065.1		c.-134T>C	upstream_gene	N/A	NP_001402994.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCAF13	ENST00000297579.9	TSL:1	c.360T>C	p.Ser120Ser	synonymous	Exon 1 of 11	ENSP00000297579.5	A0A087WT20
DCAF13	ENST00000616836.4	TSL:1	c.360T>C	p.Ser120Ser	synonymous	Exon 1 of 11	ENSP00000477526.1	A0A087WT20
ENSG00000285982	ENST00000649416.1		c.2-7566A>G		intron	N/A	ENSP00000496817.1	A0A3B3IRK5

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34346

AN:

151698

Hom.:

3995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.278

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.230

GnomAD2 exomes

AF:

0.236

AC:

59163

AN:

250596

AF XY:

0.236

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.235

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.329

Gnomad FIN exome

AF:

0.266

Gnomad NFE exome

AF:

0.221

Gnomad OTH exome

AF:

0.233

GnomAD4 exome

AF:

0.226

AC:

330644

AN:

1461774

Hom.:

38228

Cov.:

AF XY:

0.227

AC XY:

164965

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.203

AC:

6782

AN:

33480

American (AMR)

AF:

0.237

AC:

10585

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

4547

AN:

26136

East Asian (EAS)

AF:

0.360

AC:

14307

AN:

39700

South Asian (SAS)

AF:

0.246

AC:

21189

AN:

86258

European-Finnish (FIN)

AF:

0.261

AC:

13926

AN:

53324

Middle Eastern (MID)

AF:

0.162

AC:

937

AN:

5768

European-Non Finnish (NFE)

AF:

0.220

AC:

245148

AN:

1112004

Other (OTH)

AF:

0.219

AC:

13223

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

17708

35415

53123

70830

88538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8552

17104

25656

34208

42760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.226

AC:

34381

AN:

151816

Hom.:

4005

Cov.:

AF XY:

0.231

AC XY:

17144

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.212

AC:

8779

AN:

41400

American (AMR)

AF:

0.236

AC:

3606

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

609

AN:

3460

East Asian (EAS)

AF:

0.343

AC:

1770

AN:

5156

South Asian (SAS)

AF:

0.242

AC:

1161

AN:

4792

European-Finnish (FIN)

AF:

0.278

AC:

2922

AN:

10520

Middle Eastern (MID)

AF:

0.175

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.218

AC:

14817

AN:

67892

Other (OTH)

AF:

0.229

AC:

483

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1391

2781

4172

5562

6953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.217

Hom.:

4320

Bravo

AF:

0.223

Asia WGS

AF:

0.306

AC:

1064

AN:

3478

EpiCase

AF:

0.219

EpiControl

AF:

0.221

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

-0.15

PromoterAI

0.026

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over