rs10435946

Positions:

• chr9-84340893-C-A
• chr9-84340893-C-G

Variant summary

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

The NM_022127.3(SLC28A3):​c.-45-215G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,830 control chromosomes in the GnomAD database, including 5,282 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 0.23 (5282 hom., cov: 30)
• Consequence: SLC28A3 NM_022127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592

Genes affected

SLC28A3 (HGNC:16484): (solute carrier family 28 member 3) Nucleoside transporters, such as SLC28A3, regulate multiple cellular processes, including neurotransmission, vascular tone, adenosine concentration in the vicinity of cell surface receptors, and transport and metabolism of nucleoside drugs. SLC28A3 shows broad specificity for pyrimidine and purine nucleosides (Ritzel et al., 2001 [PubMed 11032837]).[supplied by OMIM, Mar 2008]

ENSG00000285987 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC28A3	NM_022127.3	c.-45-215G>T		intron_variant			NP_071410.1
SLC28A3	XM_011518906.3	c.-45-215G>T		intron_variant			XP_011517208.1
SLC28A3	XM_011518907.3	c.-97-27439G>T		intron_variant			XP_011517209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000285987	ENST00000650453.1	n.536+23844C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34519 AN: 151712 Hom.: 5274 Cov.: 30

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.228 AC: 34561 AN: 151830 Hom.: 5282 Cov.: 30 AF XY: 0.227 AC XY: 16816 AN XY: 74186

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.184

Alfa AF: 0.180 Hom.: 1541

Bravo AF: 0.232

Asia WGS AF: 0.255 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10435946; hg19: chr9-86955808;