dbSNP rs8187758: SLC28A1:p.Gln237Lys (chr15-84905644-C-A) – 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.709C>A(p.Gln237Lys) variant causes a missense change. The variant allele was found at a frequency of 0.25 in 1,608,760 control chromosomes in the GnomAD database, including 53,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.23 ( 4358 hom., cov: 33)

Exomes 𝑓: 0.25 ( 49387 hom. )

Consequence

SLC28A1
NM_004213.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.80

Publications

34 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=0.005893916).

BP6

Variant 15-84905644-C-A is Benign according to our data. Variant chr15-84905644-C-A is described in ClinVar as Benign. ClinVar VariationId is 3059004.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5 link	c.709C>A	p.Gln237Lys	missense_variant	Exon 8 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.709C>A	p.Gln237Lys	missense_variant	Exon 8 of 19	1	NM_004213.5	ENSP00000378074.1	O00337-1
SLC28A1	ENST00000286749.3 link	c.709C>A	p.Gln237Lys	missense_variant	Exon 7 of 18	1		ENSP00000286749.3	O00337-1
SLC28A1	ENST00000538177.5 link	c.709C>A	p.Gln237Lys	missense_variant	Exon 7 of 15	2		ENSP00000443752.1	B7Z3L6

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34972

AN:

151980

Hom.:

4345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.187

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.211

GnomAD2 exomes

AF:

0.281

AC:

70544

AN:

251152

AF XY:

0.281

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.432

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.322

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.252

AC:

366592

AN:

1456662

Hom.:

49387

Cov.:

AF XY:

0.256

AC XY:

185300

AN XY:

724882

show subpopulations

African (AFR)

AF:

0.161

AC:

5358

AN:

33378

American (AMR)

AF:

0.421

AC:

18834

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

5544

AN:

26100

East Asian (EAS)

AF:

0.322

AC:

12779

AN:

39674

South Asian (SAS)

AF:

0.422

AC:

36333

AN:

86106

European-Finnish (FIN)

AF:

0.221

AC:

11826

AN:

53406

Middle Eastern (MID)

AF:

0.204

AC:

1178

AN:

5762

European-Non Finnish (NFE)

AF:

0.235

AC:

259790

AN:

1107330

Other (OTH)

AF:

0.248

AC:

14950

AN:

60218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

13106

26212

39319

52425

65531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9242

18484

27726

36968

46210

<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:

0.230

AC:

35018

AN:

152098

Hom.:

4358

Cov.:

AF XY:

0.235

AC XY:

17455

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.170

AC:

7050

AN:

41504

American (AMR)

AF:

0.328

AC:

5012

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

739

AN:

3472

East Asian (EAS)

AF:

0.316

AC:

1624

AN:

5140

South Asian (SAS)

AF:

0.457

AC:

2201

AN:

4820

European-Finnish (FIN)

AF:

0.214

AC:

2262

AN:

10588

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15454

AN:

67990

Other (OTH)

AF:

0.214

AC:

452

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1384

2767

4151

5534

6918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<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:

0.228

Hom.:

16236

Bravo

AF:

0.232

TwinsUK

AF:

0.238

AC:

881

ALSPAC

AF:

0.249

AC:

960

ESP6500AA

AF:

0.171

AC:

752

ESP6500EA

AF:

0.224

AC:

1926

ExAC

AF:

0.273

AC:

33199

Asia WGS

AF:

0.362

AC:

1259

AN:

3478

EpiCase

AF:

0.222

EpiControl

AF:

0.225

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC28A1-related disorder

Benign:1

Nov 01, 2019

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.021

T;T;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.94

D;D;.

MetaRNN

Benign

0.0059

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.9

.;L;L

PhyloP100

5.8

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Benign

0.14

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

1.0

D;P;P

Vest4

0.40

MPC

0.49

ClinPred

0.035

GERP RS

4.0

Varity_R

0.73

gMVP

0.78

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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