rs56350726

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-84285454-T-A
• chr9-84285454-T-C

Variant summary

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

The NM_022127.3(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.

• Frequency:
  • Genomes: 𝑓 0.091 (756 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3361 hom.)
• Consequence: SLC28A3 NM_022127.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48
• Publications: 34 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]

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022127.3. 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
	SLC28A3	NM_001199633.2	MANE Select	c.1538A>T	p.Tyr513Phe	missense	Exon 14 of 18	NP_001186562.1
	SLC28A3	NM_022127.3		c.1538A>T	p.Tyr513Phe	missense	Exon 15 of 19	NP_071410.1
	SLC28A3	NR_037638.3		n.1839A>T		non_coding_transcript_exon	Exon 15 of 19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A3	ENST00000376238.5	TSL:1 MANE Select	c.1538A>T	p.Tyr513Phe	missense	Exon 14 of 18	ENSP00000365413.4
	SLC28A3-AS1	ENST00000419815.1	TSL:3	n.182-4486T>A		intron	N/A

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

African (AFR) AF: 0.150 AC: 5013 AN: 33480

American (AMR) AF: 0.0306 AC: 1368 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 1241 AN: 26136

East Asian (EAS) AF: 0.0910 AC: 3614 AN: 39698

South Asian (SAS) AF: 0.0746 AC: 6437 AN: 86256

European-Finnish (FIN) AF: 0.127 AC: 6807 AN: 53414

Middle Eastern (MID) AF: 0.0463 AC: 267 AN: 5768

European-Non Finnish (NFE) AF: 0.0576 AC: 64053 AN: 1111984

Other (OTH) 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

African (AFR) AF: 0.152 AC: 6313 AN: 41516

American (AMR) AF: 0.0482 AC: 738 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3472

East Asian (EAS) AF: 0.103 AC: 535 AN: 5174

South Asian (SAS) AF: 0.0795 AC: 384 AN: 4830

European-Finnish (FIN) AF: 0.126 AC: 1335 AN: 10584

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0604 AC: 4110 AN: 68014

Other (OTH) AF: 0.0851 AC: 180 AN: 2114

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 v4.9

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
PhyloP100		2.5
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

Other links and lift over

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