dbSNP rs10868138: SLC28A3:p.Tyr113Cys (chr9-84302386-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001199633.2(SLC28A3):c.338A>G(p.Tyr113Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 1,612,632 control chromosomes in the GnomAD database, including 6,368 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 0.11 ( 1086 hom., cov: 32)

Exomes 𝑓: 0.081 ( 5282 hom. )

Consequence

SLC28A3
NM_001199633.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.26

Publications

44 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0018907189).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A3	NM_001199633.2 link	c.338A>G	p.Tyr113Cys	missense_variant	Exon 5 of 18	ENST00000376238.5	NP_001186562.1	Q9HAS3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC28A3	ENST00000376238.5 link	c.338A>G	p.Tyr113Cys	missense_variant	Exon 5 of 18	1	NM_001199633.2	ENSP00000365413.4		Q9HAS3-1

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16770

AN:

152020

Hom.:

1079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0635

Gnomad ASJ

AF:

0.0663

Gnomad EAS

AF:

0.0820

Gnomad SAS

AF:

0.0791

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0810

Gnomad OTH

AF:

0.101

GnomAD2 exomes

AF:

0.0839

AC:

20823

AN:

248300

AF XY:

0.0835

show subpopulations

Gnomad AFR exome

AF:

0.184

Gnomad AMR exome

AF:

0.0358

Gnomad ASJ exome

AF:

0.0674

Gnomad EAS exome

AF:

0.0905

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.0768

Gnomad OTH exome

AF:

0.0815

GnomAD4 exome

AF:

0.0813

AC:

118754

AN:

1460494

Hom.:

5282

Cov.:

AF XY:

0.0807

AC XY:

58649

AN XY:

726478

show subpopulations

African (AFR)

AF:

0.179

AC:

5992

AN:

33462

American (AMR)

AF:

0.0389

AC:

1732

AN:

44554

Ashkenazi Jewish (ASJ)

AF:

0.0640

AC:

1672

AN:

26112

East Asian (EAS)

AF:

0.0781

AC:

3093

AN:

39616

South Asian (SAS)

AF:

0.0776

AC:

6683

AN:

86152

European-Finnish (FIN)

AF:

0.132

AC:

7026

AN:

53300

Middle Eastern (MID)

AF:

0.0592

AC:

331

AN:

5592

European-Non Finnish (NFE)

AF:

0.0783

AC:

86976

AN:

1111358

Other (OTH)

AF:

0.0870

AC:

5249

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

5369

10738

16106

21475

26844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3288

6576

9864

13152

16440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.110

AC:

16802

AN:

152138

Hom.:

1086

Cov.:

AF XY:

0.110

AC XY:

8196

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.184

AC:

7624

AN:

41480

American (AMR)

AF:

0.0633

AC:

968

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0663

AC:

230

AN:

3470

East Asian (EAS)

AF:

0.0818

AC:

423

AN:

5172

South Asian (SAS)

AF:

0.0802

AC:

387

AN:

4824

European-Finnish (FIN)

AF:

0.130

AC:

1379

AN:

10590

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0810

AC:

5509

AN:

67994

Other (OTH)

AF:

0.106

AC:

225

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

763

1526

2290

3053

3816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0858

Hom.:

2517

Bravo

AF:

0.108

TwinsUK

AF:

0.0828

AC:

307

ALSPAC

AF:

0.0786

AC:

303

ESP6500AA

AF:

0.174

AC:

766

ESP6500EA

AF:

0.0767

AC:

660

ExAC

AF:

0.0861

AC:

10456

Asia WGS

AF:

0.100

AC:

350

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

Eigen

Benign

-0.0079

Eigen_PC

Benign

0.044

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.95

MutationAssessor

Pathogenic

3.1

PhyloP100

2.3

PrimateAI

Uncertain

0.48

PROVEAN

Pathogenic

-6.8

REVEL

Uncertain

0.38

Sift

Uncertain

0.020

Sift4G

Uncertain

0.016

Polyphen

0.43

Vest4

0.26

MPC

0.65

ClinPred

0.098

GERP RS

2.8

Varity_R

0.71

gMVP

0.79

Mutation Taster

=81/19

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over