Variant 15-84895102-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000394573.6(SLC28A1):c.440G>A(p.Arg147His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00712 in 1,614,000 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 51 hom. )

Consequence

SLC28A1
ENST00000394573.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.0220

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055637658).

BP6

Variant 15-84895102-G-A is Benign according to our data. Variant chr15-84895102-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645652.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC28A1	NM_004213.5 linkuse as main transcript	c.440G>A	p.Arg147His	missense_variant	6/19	ENST00000394573.6	NP_004204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC28A1	ENST00000394573.6 linkuse as main transcript	c.440G>A	p.Arg147His	missense_variant	6/19	1	NM_004213.5	ENSP00000378074	P1	O00337-1
SLC28A1	ENST00000286749.3 linkuse as main transcript	c.440G>A	p.Arg147His	missense_variant	5/18	1		ENSP00000286749	P1	O00337-1
SLC28A1	ENST00000338602.6 linkuse as main transcript	c.440G>A	p.Arg147His	missense_variant	6/7	1		ENSP00000341629		O00337-2
SLC28A1	ENST00000538177.5 linkuse as main transcript	c.440G>A	p.Arg147His	missense_variant	5/15	2		ENSP00000443752

Frequencies

GnomAD3 genomes

AF:

0.00529

AC:

805

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0124

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00726

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00540

AC:

1355

AN:

250818

Hom.:

AF XY:

0.00537

AC XY:

728

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.000869

Gnomad AMR exome

AF:

0.00451

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.0124

Gnomad NFE exome

AF:

0.00755

Gnomad OTH exome

AF:

0.00556

GnomAD4 exome

AF:

0.00731

AC:

10684

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00699

AC XY:

5083

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00481

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.0111

Gnomad4 NFE exome

AF:

0.00841

Gnomad4 OTH exome

AF:

0.00699

GnomAD4 genome

AF:

0.00528

AC:

804

AN:

152290

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

399

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0124

Gnomad4 NFE

AF:

0.00726

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00656

Hom.:

Bravo

AF:

0.00458

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00675

AC:

ExAC

AF:

0.00517

AC:

628

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00692

EpiControl

AF:

0.00753

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

SLC28A1: BP4, BS2 -

SLC28A1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 13, 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

0.071

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.028

.;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.71

T;T;T;.

MetaRNN

Benign

0.0056

T;T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.5

M;.;M;M

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.094

T;T;T;T

Sift4G

Benign

0.19

T;T;T;T

Polyphen

1.0

D;B;B;B

Vest4

0.063

MVP

0.43

MPC

0.094

ClinPred

0.0059

GERP RS

0.34

Varity_R

0.033

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