Variant 15-84904200-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004213.5(SLC28A1):c.565G>A(p.Val189Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,613,866 control chromosomes in the GnomAD database, including 118,329 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.34 ( 9369 hom., cov: 33)

Exomes 𝑓: 0.38 ( 108960 hom. )

Consequence

SLC28A1
NM_004213.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.852

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.0749636E-5).

BP6

Variant 15-84904200-G-A is Benign according to our data. Variant chr15-84904200-G-A is described in ClinVar as [Benign]. Clinvar id is 3059692.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC28A1	NM_004213.5 linkuse as main transcript	c.565G>A	p.Val189Ile	missense_variant	7/19	ENST00000394573.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC28A1	ENST00000394573.6 linkuse as main transcript	c.565G>A	p.Val189Ile	missense_variant	7/19	1	NM_004213.5	P1	O00337-1
SLC28A1	ENST00000286749.3 linkuse as main transcript	c.565G>A	p.Val189Ile	missense_variant	6/18	1		P1	O00337-1
SLC28A1	ENST00000538177.5 linkuse as main transcript	c.565G>A	p.Val189Ile	missense_variant	6/15	2

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51482

AN:

151998

Hom.:

9354

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.553

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.327

GnomAD3 exomes

AF:

0.403

AC:

101384

AN:

251380

Hom.:

22006

AF XY:

0.404

AC XY:

54898

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.578

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.396

Gnomad SAS exome

AF:

0.531

Gnomad FIN exome

AF:

0.400

Gnomad NFE exome

AF:

0.353

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.381

AC:

556305

AN:

1461750

Hom.:

108960

Cov.:

AF XY:

0.385

AC XY:

279657

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.567

Gnomad4 ASJ exome

AF:

0.313

Gnomad4 EAS exome

AF:

0.401

Gnomad4 SAS exome

AF:

0.524

Gnomad4 FIN exome

AF:

0.406

Gnomad4 NFE exome

AF:

0.368

Gnomad4 OTH exome

AF:

0.368

GnomAD4 genome

AF:

0.339

AC:

51522

AN:

152116

Hom.:

9369

Cov.:

AF XY:

0.346

AC XY:

25710

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.462

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.393

Gnomad4 SAS

AF:

0.554

Gnomad4 FIN

AF:

0.408

Gnomad4 NFE

AF:

0.358

Gnomad4 OTH

AF:

0.328

Alfa

AF:

0.350

Hom.:

19427

Bravo

AF:

0.334

TwinsUK

AF:

0.374

AC:

1387

ALSPAC

AF:

0.378

AC:

1458

ESP6500AA

AF:

0.218

AC:

962

ESP6500EA

AF:

0.350

AC:

3013

ExAC

AF:

0.391

AC:

47489

Asia WGS

AF:

0.439

AC:

1525

AN:

3478

EpiCase

AF:

0.351

EpiControl

AF:

0.353

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SLC28A1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

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

0.063

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

Cadd

Benign

0.0030

Dann

Benign

0.29

DEOGEN2

Benign

0.0050

T;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0074

LIST_S2

Benign

0.087

T;T;.

MetaRNN

Benign

0.000021

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Benign

0.44

PROVEAN

Benign

0.44

N;N;N

REVEL

Benign

0.020

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.035

B;B;B

Vest4

0.037

MPC

0.063

ClinPred

0.0021

GERP RS

-5.9

Varity_R

0.030

gMVP

0.12

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