9-84305321-T-C

Variant names:

• chr9-84305321-T-C
• rs7867504
• NM_001199633.2:c.267A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001199633.2(SLC28A3):​c.267A>G​(p.Thr89Thr) 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
• Publications: 39 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC28A3	NM_001199633.2	c.267A>G	p.Thr89Thr	synonymous_variant	Exon 4 of 18	ENST00000376238.5	NP_001186562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC28A3	ENST00000376238.5	c.267A>G	p.Thr89Thr	synonymous_variant	Exon 4 of 18	1	NM_001199633.2	ENSP00000365413.4
SLC28A3	ENST00000495823.1	n.469A>G		non_coding_transcript_exon_variant	Exon 5 of 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

GnomAD2 exomes AF: 0.407 AC: 101719 AN: 250042 AF XY: 0.387

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 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

African (AFR) AF: 0.760 AC: 25380 AN: 33414

American (AMR) AF: 0.607 AC: 27019 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 9261 AN: 26120

East Asian (EAS) AF: 0.586 AC: 23227 AN: 39666

South Asian (SAS) AF: 0.384 AC: 32890 AN: 85684

European-Finnish (FIN) AF: 0.284 AC: 15158 AN: 53388

Middle Eastern (MID) AF: 0.321 AC: 1850 AN: 5766

European-Non Finnish (NFE) AF: 0.298 AC: 331064 AN: 1111120

Other (OTH) AF: 0.369 AC: 22277 AN: 60338

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

African (AFR) AF: 0.750 AC: 31081 AN: 41436

American (AMR) AF: 0.519 AC: 7918 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1257 AN: 3470

East Asian (EAS) AF: 0.602 AC: 3100 AN: 5150

South Asian (SAS) AF: 0.398 AC: 1914 AN: 4808

European-Finnish (FIN) AF: 0.277 AC: 2917 AN: 10542

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20302 AN: 67986

Other (OTH) AF: 0.441 AC: 929 AN: 2108

Alfa AF: 0.358 Hom.: 49951

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
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7867504; hg19: chr9-86920236; COSMIC: COSV66152112;