20-46354878-G-A

Variant names:

• chr20-46354878-G-A
• rs12480667
• NM_015945.12:c.661+4C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015945.12(SLC35H1):​c.661+4C>T variant causes a splice 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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: SLC35H1 NM_015945.12 splice_region, intron
• Scores: Splicing: ADA: 0.0001227
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 12 publications found

Genes affected

SLC35H1 (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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015945.12. 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
	SLC35H1	NM_015945.12	MANE Select	c.661+4C>T		splice_region intron	N/A	NP_057029.8
	SLC35H1	NM_001281458.2		c.748+4C>T		splice_region intron	N/A	NP_001268387.1
	SLC35H1	NM_001281460.2		c.661+4C>T		splice_region intron	N/A	NP_001268389.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C2	ENST00000372230.10	TSL:1 MANE Select	c.661+4C>T		splice_region intron	N/A	ENSP00000361304.5
	SLC35C2	ENST00000243896.6	TSL:1	c.661+4C>T		splice_region intron	N/A	ENSP00000243896.2
	SLC35C2	ENST00000372227.5	TSL:1	c.661+4C>T		splice_region intron	N/A	ENSP00000361301.1

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

GnomAD2 exomes AF: 0.234 AC: 50625 AN: 216380 AF XY: 0.234

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 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

African (AFR) AF: 0.0405 AC: 1345 AN: 33226

American (AMR) AF: 0.312 AC: 12523 AN: 40120

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 4651 AN: 25694

East Asian (EAS) AF: 0.0754 AC: 2933 AN: 38896

South Asian (SAS) AF: 0.199 AC: 16709 AN: 84114

European-Finnish (FIN) AF: 0.307 AC: 15984 AN: 51994

Middle Eastern (MID) AF: 0.195 AC: 1120 AN: 5740

European-Non Finnish (NFE) AF: 0.267 AC: 294151 AN: 1101008

Other (OTH) AF: 0.223 AC: 13310 AN: 59620

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

African (AFR) AF: 0.0509 AC: 2117 AN: 41566

American (AMR) AF: 0.246 AC: 3769 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3470

East Asian (EAS) AF: 0.0682 AC: 353 AN: 5178

South Asian (SAS) AF: 0.193 AC: 930 AN: 4812

European-Finnish (FIN) AF: 0.326 AC: 3444 AN: 10562

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18300 AN: 67964

Other (OTH) AF: 0.179 AC: 378 AN: 2108

Alfa AF: 0.238 Hom.: 7145

Bravo AF: 0.187

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.28
DANN	Benign	0.79
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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