Genetic Variant SLC28A2:p.Pro22Leu (chr15-45253280-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_004212.4(SLC28A2):c.65C>T(p.Pro22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,610,236 control chromosomes in the GnomAD database, including 279,892 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 0.45 ( 18965 hom., cov: 32)

Exomes 𝑓: 0.58 ( 260927 hom. )

Consequence

SLC28A2
NM_004212.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.79

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=7.6209626E-6).

BP6

Variant 15-45253280-C-T is Benign according to our data. Variant chr15-45253280-C-T is described in ClinVar as [Benign]. Clinvar id is 1269551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A2	NM_004212.4 link	c.65C>T	p.Pro22Leu	missense_variant	Exon 2 of 18	ENST00000347644.8	NP_004203.2	O43868Q2M2A7Q53H72
SLC28A2-AS1	NR_120335.1 link	n.180+586G>A		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC28A2	ENST00000347644.8 link	c.65C>T	p.Pro22Leu	missense_variant	Exon 2 of 18	1	NM_004212.4	ENSP00000315006.4		O43868

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68700

AN:

151942

Hom.:

18972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.722

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.0875

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.594

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.635

Gnomad OTH

AF:

0.468

GnomAD3 exomes

AF:

0.474

AC:

118542

AN:

250026

Hom.:

32517

AF XY:

0.491

AC XY:

66311

AN XY:

135038

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.282

Gnomad ASJ exome

AF:

0.510

Gnomad EAS exome

AF:

0.0793

Gnomad SAS exome

AF:

0.454

Gnomad FIN exome

AF:

0.582

Gnomad NFE exome

AF:

0.620

Gnomad OTH exome

AF:

0.528

GnomAD4 exome

AF:

0.582

AC:

848558

AN:

1458176

Hom.:

260927

Cov.:

AF XY:

0.581

AC XY:

421374

AN XY:

725480

show subpopulations

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.299

Gnomad4 ASJ exome

AF:

0.512

Gnomad4 EAS exome

AF:

0.0627

Gnomad4 SAS exome

AF:

0.464

Gnomad4 FIN exome

AF:

0.588

Gnomad4 NFE exome

AF:

0.638

Gnomad4 OTH exome

AF:

0.543

GnomAD4 genome

AF:

0.452

AC:

68704

AN:

152060

Hom.:

18965

Cov.:

AF XY:

0.445

AC XY:

33086

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.387

Gnomad4 ASJ

AF:

0.505

Gnomad4 EAS

AF:

0.0874

Gnomad4 SAS

AF:

0.431

Gnomad4 FIN

AF:

0.594

Gnomad4 NFE

AF:

0.635

Gnomad4 OTH

AF:

0.463

Alfa

AF:

0.567

Hom.:

43884

Bravo

AF:

0.421

TwinsUK

AF:

0.644

AC:

2387

ALSPAC

AF:

0.631

AC:

2433

ESP6500AA

AF:

0.191

AC:

840

ESP6500EA

AF:

0.628

AC:

5402

ExAC

AF:

0.474

AC:

57598

Asia WGS

AF:

0.265

AC:

922

AN:

3478

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

0.074

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.7

DANN

Benign

0.71

DEOGEN2

Benign

0.020

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0000076

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.13

REVEL

Benign

0.056

Sift

Benign

0.55

Sift4G

Benign

0.32

Polyphen

0.0010

Vest4

0.042

MPC

0.042

ClinPred

0.0066

GERP RS

-0.81

Varity_R

0.023

gMVP

0.16

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

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