rs12480667

chr20-46354878-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015945.12(SLC35C2):c.661+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,592,576 control chromosomes in the GnomAD database, including 51,735 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3902 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47833 hom.)
• Consequence: SLC35C2 NM_015945.12 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0001227
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

Genes affected

SLC35C2 (HGNC:17117): (solute carrier family 35 member C2) This gene encodes a member of the triose-phosphate transporter protein family. This gene is regulated by oxygen tension, is induced in hypoxic trophoblast cells, and is overexpressed in ovarian cancer. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been defined on the X chromosome. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35C2	NM_015945.12	c.661+4C>T		splice_donor_region_variant, intron_variant		ENST00000372230.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35C2	ENST00000372230.10	c.661+4C>T		splice_donor_region_variant, intron_variant		1	NM_015945.12	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30370 AN: 152046 Hom.: 3908 Cov.: 32

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.182

GnomAD3 exomes AF: 0.234 AC: 50625 AN: 216380 Hom.: 6676 AF XY: 0.234 AC XY: 27237 AN XY: 116330

Gnomad AFR exome AF: 0.0435

Gnomad AMR exome AF: 0.314

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.0644

Gnomad SAS exome AF: 0.200

Gnomad FIN exome AF: 0.317

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.252 AC: 362726 AN: 1440412 Hom.: 47833 Cov.: 33 AF XY: 0.250 AC XY: 178908 AN XY: 714852

Gnomad4 AFR exome AF: 0.0405

Gnomad4 AMR exome AF: 0.312

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.0754

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.199 AC: 30351 AN: 152164 Hom.: 3902 Cov.: 32 AF XY: 0.201 AC XY: 14984 AN XY: 74368

Gnomad4 AFR AF: 0.0509

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.0682

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.179

Alfa AF: 0.236 Hom.: 4866

Bravo AF: 0.187

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.28
Dann	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.026
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

Other links and lift over

dbSNP: rs12480667; hg19: chr20-44983517; COSMIC: COSV54758748; COSMIC: COSV54758748;