20-46358679-C-G

Variant names:

• chr20-46358679-C-G
• rs1044369
• NM_015945.12:c.-173G>C

Variant summary

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

The NM_015945.12(SLC35H1):​c.-173G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,551,074 control chromosomes in the GnomAD database, including 70,098 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 0.24 (5435 hom., cov: 32)
  • Exomes 𝑓: 0.30 (64663 hom.)
• Consequence: SLC35H1 NM_015945.12 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520
• Publications: 14 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35H1	NM_015945.12	MANE Select	c.-173G>C		5_prime_UTR	Exon 2 of 10	NP_057029.8
	SLC35H1	NM_001281460.2		c.-173G>C		5_prime_UTR	Exon 3 of 11	NP_001268389.1	Q9NQQ7-1
	SLC35H1	NM_173179.4		c.-173G>C		5_prime_UTR	Exon 2 of 10	NP_775271.1	Q9NQQ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C2	ENST00000372230.10	TSL:1 MANE Select	c.-173G>C		5_prime_UTR	Exon 2 of 10	ENSP00000361304.5	Q9NQQ7-1
	SLC35C2	ENST00000243896.6	TSL:1	c.-173G>C		5_prime_UTR	Exon 2 of 10	ENSP00000243896.2	Q9NQQ7-1
	SLC35C2	ENST00000372227.5	TSL:1	c.-173G>C		5_prime_UTR	Exon 2 of 10	ENSP00000361301.1	Q9NQQ7-1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35974 AN: 152034 Hom.: 5442 Cov.: 32

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.0734

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.228

GnomAD2 exomes AF: 0.287 AC: 44249 AN: 154426 AF XY: 0.287

Gnomad AFR exome AF: 0.0517

Gnomad AMR exome AF: 0.335

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.0688

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.315

Gnomad OTH exome AF: 0.291

GnomAD4 exome AF: 0.298 AC: 416749 AN: 1398922 Hom.: 64663 Cov.: 36 AF XY: 0.298 AC XY: 205526 AN XY: 689990

African (AFR) AF: 0.0522 AC: 1650 AN: 31598

American (AMR) AF: 0.333 AC: 11900 AN: 35720

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 6200 AN: 25182

East Asian (EAS) AF: 0.0798 AC: 2853 AN: 35738

South Asian (SAS) AF: 0.281 AC: 22305 AN: 79278

European-Finnish (FIN) AF: 0.380 AC: 18562 AN: 48796

Middle Eastern (MID) AF: 0.276 AC: 1574 AN: 5698

European-Non Finnish (NFE) AF: 0.312 AC: 336142 AN: 1078906

Other (OTH) AF: 0.268 AC: 15563 AN: 58006

GnomAD4 genome AF: 0.236 AC: 35955 AN: 152152 Hom.: 5435 Cov.: 32 AF XY: 0.239 AC XY: 17783 AN XY: 74382

African (AFR) AF: 0.0632 AC: 2627 AN: 41538

American (AMR) AF: 0.276 AC: 4216 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 850 AN: 3472

East Asian (EAS) AF: 0.0732 AC: 379 AN: 5178

South Asian (SAS) AF: 0.269 AC: 1294 AN: 4812

European-Finnish (FIN) AF: 0.396 AC: 4196 AN: 10584

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21422 AN: 67964

Other (OTH) AF: 0.225 AC: 475 AN: 2112

Alfa AF: 0.210 Hom.: 789

Bravo AF: 0.218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-0.52
PromoterAI		-0.00020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1044369; hg19: chr20-44987318; COSMIC: COSV54758762; COSMIC: COSV54758762;