Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001199633.2(SLC28A3):c.1381C>T(p.Leu461Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,680 control chromosomes in the GnomAD database, including 19,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3142 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16505 hom. )

Consequence

SLC28A3
NM_001199633.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.773

Publications

113 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:

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

SLC28A3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 9-84286011-G-A is Benign according to our data. Variant chr9-84286011-G-A is described in ClinVar as Benign. ClinVar VariationId is 375669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.773 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199633.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC28A3	NM_001199633.2	MANE Select	c.1381C>T	p.Leu461Leu	synonymous	Exon 13 of 18	NP_001186562.1
SLC28A3	NM_022127.3		c.1381C>T	p.Leu461Leu	synonymous	Exon 14 of 19	NP_071410.1
SLC28A3	NR_037638.3		n.1682C>T		non_coding_transcript_exon	Exon 14 of 19

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A3	ENST00000376238.5	TSL:1 MANE Select	c.1381C>T	p.Leu461Leu	synonymous	Exon 13 of 18	ENSP00000365413.4
	SLC28A3-AS1	ENST00000419815.1	TSL:3	n.182-3929G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28410

AN:

152030

Hom.:

3136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0605

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.191

GnomAD2 exomes

AF:

0.153

AC:

38437

AN:

250790

AF XY:

0.147

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.0663

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.145

AC:

211832

AN:

1461532

Hom.:

16505

Cov.:

AF XY:

0.144

AC XY:

104536

AN XY:

727050

show subpopulations

African (AFR)

AF:

0.322

AC:

10792

AN:

33470

American (AMR)

AF:

0.201

AC:

8965

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

5632

AN:

26130

East Asian (EAS)

AF:

0.116

AC:

4597

AN:

39692

South Asian (SAS)

AF:

0.128

AC:

11079

AN:

86220

European-Finnish (FIN)

AF:

0.0702

AC:

3750

AN:

53410

Middle Eastern (MID)

AF:

0.152

AC:

874

AN:

5766

European-Non Finnish (NFE)

AF:

0.140

AC:

156101

AN:

1111786

Other (OTH)

AF:

0.166

AC:

10042

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

9356

18712

28069

37425

46781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5788

11576

17364

23152

28940

<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:

0.187

AC:

28460

AN:

152148

Hom.:

3142

Cov.:

AF XY:

0.180

AC XY:

13410

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.308

AC:

12770

AN:

41458

American (AMR)

AF:

0.188

AC:

2868

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

771

AN:

3470

East Asian (EAS)

AF:

0.149

AC:

770

AN:

5184

South Asian (SAS)

AF:

0.132

AC:

638

AN:

4826

European-Finnish (FIN)

AF:

0.0605

AC:

642

AN:

10608

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.140

AC:

9505

AN:

67996

Other (OTH)

AF:

0.190

AC:

401

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1121

2242

3363

4484

5605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.161

Hom.:

8578

Bravo

AF:

0.203

Asia WGS

AF:

0.163

AC:

568

AN:

3478

EpiCase

AF:

0.144

EpiControl

AF:

0.143

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.2

(source)

DANN

Benign

0.63

PhyloP100

0.77

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over