9-84305321-T-C

Position:

• chr9-84305321-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001199633.2(SLC28A3):​c.267A>G​(p.Thr89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,611,954 control chromosomes in the GnomAD database, including 108,473 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 0.46 (19026 hom., cov: 31)
  • Exomes 𝑓: 0.33 (89447 hom.)
• Consequence: SLC28A3 NM_001199633.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-1.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC28A3	NM_001199633.2	c.267A>G	p.Thr89=	synonymous_variant	4/18	ENST00000376238.5	NP_001186562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC28A3	ENST00000376238.5	c.267A>G	p.Thr89=	synonymous_variant	4/18	1	NM_001199633.2	ENSP00000365413	P1
SLC28A3	ENST00000495823.1	n.469A>G		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69478 AN: 151848 Hom.: 18959 Cov.: 31

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.440

GnomAD3 exomes AF: 0.407 AC: 101719 AN: 250042 Hom.: 24068 AF XY: 0.387 AC XY: 52278 AN XY: 135034

Gnomad AFR exome AF: 0.756

Gnomad AMR exome AF: 0.625

Gnomad ASJ exome AF: 0.359

Gnomad EAS exome AF: 0.612

Gnomad SAS exome AF: 0.385

Gnomad FIN exome AF: 0.284

Gnomad NFE exome AF: 0.293

Gnomad OTH exome AF: 0.369

GnomAD4 exome AF: 0.334 AC: 488126 AN: 1459992 Hom.: 89447 Cov.: 38 AF XY: 0.332 AC XY: 241286 AN XY: 726206

Gnomad4 AFR exome AF: 0.760

Gnomad4 AMR exome AF: 0.607

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.586

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.458 AC: 69612 AN: 151962 Hom.: 19026 Cov.: 31 AF XY: 0.457 AC XY: 33910 AN XY: 74278

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.441

Alfa AF: 0.337 Hom.: 22123

Bravo AF: 0.491

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.81
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs7867504; hg19: chr9-86920236; COSMIC: COSV66152112;