15-45262069-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004212.4(SLC28A2):c.225C>A(p.Ser75Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,610,694 control chromosomes in the GnomAD database, including 308,023 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.47 ( 20716 hom., cov: 31)

Exomes 𝑓: 0.61 ( 287307 hom. )

Consequence

SLC28A2
NM_004212.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.37

Variant links:

Genes affected

SLC28A2 (HGNC:11002): (solute carrier family 28 member 2) Enables neurotransmitter transmembrane transporter activity and nucleoside transmembrane transporter activity. Involved in several processes, including nucleoside transport; purine nucleobase transmembrane transport; and pyrimidine-containing compound transmembrane transport. Predicted to be located in membrane. Predicted to be part of brush border membrane; coated vesicle; and vesicle membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC28A2 links:

SLC28A2-AS1 (HGNC:55417): (SLC28A2 antisense RNA 1)

SLC28A2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.6951517E-6).

BP6

Variant 15-45262069-C-A is Benign according to our data. Variant chr15-45262069-C-A is described in ClinVar as [Benign]. Clinvar id is 1267759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A2	NM_004212.4 link	c.225C>A	p.Ser75Arg	missense_variant	Exon 4 of 18	ENST00000347644.8	NP_004203.2	O43868Q2M2A7Q53H72
SLC28A2-AS1	NR_120335.1 link	n.27-6071G>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC28A2	ENST00000347644.8 link	c.225C>A	p.Ser75Arg	missense_variant	Exon 4 of 18	1	NM_004212.4	ENSP00000315006.4		O43868

Frequencies

GnomAD3 genomes

AF:

0.473

AC:

71905

AN:

151958

Hom.:

20722

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.748

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.0958

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.601

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.665

Gnomad OTH

AF:

0.490

GnomAD3 exomes

AF:

0.501

AC:

125660

AN:

251060

Hom.:

36498

AF XY:

0.518

AC XY:

70311

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.173

Gnomad AMR exome

AF:

0.300

Gnomad ASJ exome

AF:

0.584

Gnomad EAS exome

AF:

0.0855

Gnomad SAS exome

AF:

0.478

Gnomad FIN exome

AF:

0.592

Gnomad NFE exome

AF:

0.653

Gnomad OTH exome

AF:

0.561

GnomAD4 exome

AF:

0.611

AC:

890706

AN:

1458618

Hom.:

287307

Cov.:

AF XY:

0.610

AC XY:

442642

AN XY:

725744

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.317

Gnomad4 ASJ exome

AF:

0.585

Gnomad4 EAS exome

AF:

0.0665

Gnomad4 SAS exome

AF:

0.487

Gnomad4 FIN exome

AF:

0.597

Gnomad4 NFE exome

AF:

0.669

Gnomad4 OTH exome

AF:

0.572

GnomAD4 genome

AF:

0.473

AC:

71898

AN:

152076

Hom.:

20716

Cov.:

AF XY:

0.464

AC XY:

34527

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.408

Gnomad4 ASJ

AF:

0.581

Gnomad4 EAS

AF:

0.0956

Gnomad4 SAS

AF:

0.452

Gnomad4 FIN

AF:

0.601

Gnomad4 NFE

AF:

0.665

Gnomad4 OTH

AF:

0.485

Alfa

AF:

0.598

Hom.:

36752

Bravo

AF:

0.443

TwinsUK

AF:

0.672

AC:

2493

ALSPAC

AF:

0.663

AC:

2555

ESP6500AA

AF:

0.196

AC:

861

ESP6500EA

AF:

0.665

AC:

5714

ExAC

AF:

0.502

AC:

60912

Asia WGS

AF:

0.279

AC:

971

AN:

3478

EpiCase

AF:

0.654

EpiControl

AF:

0.651

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30315176) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

0.21

DANN

Benign

0.87

DEOGEN2

Benign

0.0067

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.11

T;T

MetaRNN

Benign

0.0000057

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.26

N;.

PrimateAI

Benign

0.21

PROVEAN

Benign

0.28

N;N

REVEL

Uncertain

0.35

Sift

Benign

0.56

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.0

B;.

Vest4

0.050

MutPred

0.16

Gain of MoRF binding (P = 0.0107);.;

MPC

0.044

ClinPred

0.0013

GERP RS

-3.7

Varity_R

0.052

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over