rs3134297

Variant names:

• chr8-103415350-T-C
• rs3134297
• ENST00000297579.9:c.360T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.148
• Publications: 16 publications found

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]

ENSG00000285982 (HGNC:):

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: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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

Selected	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
	DCAF13	ENST00000616836.4	TSL:1	c.360T>C	p.Ser120Ser	synonymous	Exon 1 of 11	ENSP00000477526.1
	ENSG00000285982	ENST00000649416.1		c.2-7566A>G		intron	N/A	ENSP00000496817.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34346 AN: 151698 Hom.: 3995 Cov.: 32

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

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.: 36 AF XY: 0.227 AC XY: 164965 AN XY: 727194

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

GnomAD4 genome AF: 0.226 AC: 34381 AN: 151816 Hom.: 4005 Cov.: 32 AF XY: 0.231 AC XY: 17144 AN XY: 74186

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: 51 AN: 292

European-Non Finnish (NFE) AF: 0.218 AC: 14817 AN: 67892

Other (OTH) AF: 0.229 AC: 483 AN: 2112

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 as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		-0.15
PromoterAI		0.026	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3134297; hg19: chr8-104427578; COSMIC: COSV52567602; COSMIC: COSV52567602;