9-84285454-T-A

Variant names:

• chr9-84285454-T-A
• rs56350726
• NM_001199633.2:c.1538A>T

Variant summary

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

The NM_001199633.2(SLC28A3):​c.1538A>T​(p.Tyr513Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0661 in 1,614,062 control chromosomes in the GnomAD database, including 4,117 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.091 (756 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3361 hom.)
• Consequence: SLC28A3 NM_001199633.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48

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]

SLC28A3-AS1 (HGNC:55460): (SLC28A3 regulatory antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004617244).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A3	NM_001199633.2	c.1538A>T	p.Tyr513Phe	missense_variant	Exon 14 of 18	ENST00000376238.5	NP_001186562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC28A3	ENST00000376238.5	c.1538A>T	p.Tyr513Phe	missense_variant	Exon 14 of 18	1	NM_001199633.2	ENSP00000365413.4
SLC28A3-AS1	ENST00000419815.1	n.182-4486T>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13785 AN: 152090 Hom.: 752 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0784

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0605

Gnomad OTH AF: 0.0798

GnomAD2 exomes AF: 0.0724 AC: 18178 AN: 251240 AF XY: 0.0723

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.0282

Gnomad ASJ exome AF: 0.0492

Gnomad EAS exome AF: 0.114

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0581

Gnomad OTH exome AF: 0.0697

GnomAD4 exome AF: 0.0636 AC: 92958 AN: 1461854 Hom.: 3361 Cov.: 32 AF XY: 0.0636 AC XY: 46236 AN XY: 727220

Gnomad4 AFR exome AF: 0.150 AC: 5013 AN: 33480

Gnomad4 AMR exome AF: 0.0306 AC: 1368 AN: 44722

Gnomad4 ASJ exome AF: 0.0475 AC: 1241 AN: 26136

Gnomad4 EAS exome AF: 0.0910 AC: 3614 AN: 39698

Gnomad4 SAS exome AF: 0.0746 AC: 6437 AN: 86256

Gnomad4 FIN exome AF: 0.127 AC: 6807 AN: 53414

Gnomad4 NFE exome AF: 0.0576 AC: 64053 AN: 1111984

Gnomad4 Remaining exome AF: 0.0688 AC: 4158 AN: 60396

GnomAD4 genome AF: 0.0907 AC: 13809 AN: 152208 Hom.: 756 Cov.: 32 AF XY: 0.0923 AC XY: 6864 AN XY: 74404

Gnomad4 AFR AF: 0.152 AC: 0.152062 AN: 0.152062

Gnomad4 AMR AF: 0.0482 AC: 0.0482416 AN: 0.0482416

Gnomad4 ASJ AF: 0.0490 AC: 0.0489631 AN: 0.0489631

Gnomad4 EAS AF: 0.103 AC: 0.103402 AN: 0.103402

Gnomad4 SAS AF: 0.0795 AC: 0.0795031 AN: 0.0795031

Gnomad4 FIN AF: 0.126 AC: 0.126134 AN: 0.126134

Gnomad4 NFE AF: 0.0604 AC: 0.0604287 AN: 0.0604287

Gnomad4 OTH AF: 0.0851 AC: 0.0851466 AN: 0.0851466

Alfa AF: 0.0564 Hom.: 223

Bravo AF: 0.0874

TwinsUK AF: 0.0607 AC: 225

ALSPAC AF: 0.0576 AC: 222

ESP6500AA AF: 0.147 AC: 647

ESP6500EA AF: 0.0571 AC: 491

ExAC AF: 0.0746 AC: 9054

Asia WGS AF: 0.100 AC: 352 AN: 3478

EpiCase AF: 0.0533

EpiControl AF: 0.0501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.97	D
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.083
Sift	Benign	0.26	T
Sift4G	Benign	0.44	T
Polyphen		0.90	P
Vest4		0.16
MPC		0.68
ClinPred		0.083	T
GERP RS		5.7
Varity_R		0.46
gMVP		0.56
Mutation Taster		=82/18	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs56350726; hg19: chr9-86900369; COSMIC: COSV66153077;