Genetic Variant SLC28A1:p.Arg510Cys (chr15-84935465-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_004213.5(SLC28A1):c.1528C>T(p.Arg510Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0351 in 1,614,108 control chromosomes in the GnomAD database, including 3,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,Affects (no stars).

Frequency

Genomes: 𝑓 0.051 ( 534 hom., cov: 32)

Exomes 𝑓: 0.033 ( 3459 hom. )

Consequence

SLC28A1
NM_004213.5 missense

Scores

Clinical Significance

Benign; Affects no assertion criteria provided B:1O:1

Conservation

PhyloP100: 3.75

Publications

24 publications found

Variant links:

Genes affected

SLC28A1 (HGNC:11001): (solute carrier family 28 member 1) Enables azole transmembrane transporter activity; cytidine transmembrane transporter activity; and uridine transmembrane transporter activity. Involved in azole transmembrane transport; nucleoside transport; and pyrimidine-containing compound transmembrane transport. Located in cytosol; nuclear speck; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC28A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031405985).

BP6

Variant 15-84935465-C-T is Benign according to our data. Variant chr15-84935465-C-T is described in ClinVar as Benign|Affects. ClinVar VariationId is 634888.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5 link	c.1528C>T	p.Arg510Cys	missense_variant	Exon 15 of 19	ENST00000394573.6	NP_004204.3	O00337-1B7Z3L5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC28A1	ENST00000394573.6 link	c.1528C>T	p.Arg510Cys	missense_variant	Exon 15 of 19	1	NM_004213.5	ENSP00000378074.1	O00337-1
SLC28A1	ENST00000286749.3 link	c.1528C>T	p.Arg510Cys	missense_variant	Exon 14 of 18	1		ENSP00000286749.3	O00337-1
SLC28A1	ENST00000538177.5 link	c.1084-7980C>T		intron_variant	Intron 11 of 14	2		ENSP00000443752.1	B7Z3L6

Frequencies

GnomAD3 genomes

AF:

0.0510

AC:

7766

AN:

152168

Hom.:

536

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0831

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0294

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.357

Gnomad SAS

AF:

0.0931

Gnomad FIN

AF:

0.0165

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0493

GnomAD2 exomes

AF:

0.0583

AC:

14656

AN:

251410

AF XY:

0.0580

show subpopulations

Gnomad AFR exome

AF:

0.0811

Gnomad AMR exome

AF:

0.0216

Gnomad ASJ exome

AF:

0.0652

Gnomad EAS exome

AF:

0.360

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.0160

Gnomad OTH exome

AF:

0.0505

GnomAD4 exome

AF:

0.0334

AC:

48872

AN:

1461822

Hom.:

3459

Cov.:

AF XY:

0.0347

AC XY:

25260

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.0800

AC:

2680

AN:

33480

American (AMR)

AF:

0.0231

AC:

1031

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0617

AC:

1612

AN:

26134

East Asian (EAS)

AF:

0.350

AC:

13905

AN:

39698

South Asian (SAS)

AF:

0.0916

AC:

7899

AN:

86256

European-Finnish (FIN)

AF:

0.0128

AC:

681

AN:

53388

Middle Eastern (MID)

AF:

0.0397

AC:

229

AN:

5768

European-Non Finnish (NFE)

AF:

0.0159

AC:

17720

AN:

1111978

Other (OTH)

AF:

0.0516

AC:

3115

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

2683

5366

8050

10733

13416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

992

1984

2976

3968

4960

<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:

0.0510

AC:

7770

AN:

152286

Hom.:

534

Cov.:

AF XY:

0.0538

AC XY:

4008

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0831

AC:

3453

AN:

41542

American (AMR)

AF:

0.0293

AC:

449

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

228

AN:

3470

East Asian (EAS)

AF:

0.357

AC:

1844

AN:

5168

South Asian (SAS)

AF:

0.0935

AC:

452

AN:

4832

European-Finnish (FIN)

AF:

0.0165

AC:

175

AN:

10618

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0152

AC:

1033

AN:

68028

Other (OTH)

AF:

0.0483

AC:

102

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

346

692

1037

1383

1729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0310

Hom.:

1009

Bravo

AF:

0.0536

TwinsUK

AF:

0.0151

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.0853

AC:

376

ESP6500EA

AF:

0.0174

AC:

150

ExAC

AF:

0.0590

AC:

7159

Asia WGS

AF:

0.204

AC:

710

AN:

3478

ClinVar

Significance: Benign; Affects

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC28A1-related disorder

Benign:1

Jan 28, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Uridine-cytidineuria

Other:1

Aug 06, 2021

OMIM

Significance:Affects

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.096

T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.16

T;.

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

M;M

PhyloP100

3.8

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.054

T;T

Polyphen

1.0

D;D

Vest4

0.17

MPC

0.51

ClinPred

0.035

GERP RS

4.1

Varity_R

0.14

gMVP

0.59

Mutation Taster

=82/18

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over