Variant 15-84904203-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004213.5(SLC28A1):c.568G>T(p.Ala190Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,614,092 control chromosomes in the GnomAD database, including 155 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 (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.013 ( 19 hom., cov: 33)

Exomes 𝑓: 0.013 ( 136 hom. )

Consequence

SLC28A1
NM_004213.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.60

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058966577).

BP6

Variant 15-84904203-G-T is Benign according to our data. Variant chr15-84904203-G-T is described in ClinVar as [Benign]. Clinvar id is 3041811.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1943/152312) while in subpopulation AFR AF= 0.0166 (689/41554). AF 95% confidence interval is 0.0156. There are 19 homozygotes in gnomad4. There are 849 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC28A1	NM_004213.5 linkuse as main transcript	c.568G>T	p.Ala190Ser	missense_variant	7/19	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.568G>T	p.Ala190Ser	missense_variant	7/19	1	NM_004213.5	ENSP00000378074	P1	O00337-1
SLC28A1	ENST00000286749.3 linkuse as main transcript	c.568G>T	p.Ala190Ser	missense_variant	6/18	1		ENSP00000286749	P1	O00337-1
SLC28A1	ENST00000538177.5 linkuse as main transcript	c.568G>T	p.Ala190Ser	missense_variant	6/15	2		ENSP00000443752

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1940

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0166

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.00971

AC:

2440

AN:

251392

Hom.:

AF XY:

0.00918

AC XY:

1247

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.0161

Gnomad AMR exome

AF:

0.00882

Gnomad ASJ exome

AF:

0.00913

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00107

Gnomad NFE exome

AF:

0.0144

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0128

AC:

18746

AN:

1461780

Hom.:

136

Cov.:

AF XY:

0.0123

AC XY:

8960

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0173

Gnomad4 AMR exome

AF:

0.00955

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.000680

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.00156

Gnomad4 NFE exome

AF:

0.0148

Gnomad4 OTH exome

AF:

0.0130

GnomAD4 genome

AF:

0.0128

AC:

1943

AN:

152312

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

849

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0166

Gnomad4 AMR

AF:

0.0155

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.0133

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.0146

TwinsUK

AF:

0.0165

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.0138

AC:

ESP6500EA

AF:

0.0144

AC:

124

ExAC

AF:

0.00923

AC:

1121

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0131

EpiControl

AF:

0.0154

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC28A1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 08, 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

0.089

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.0010

DANN

Benign

0.66

DEOGEN2

Benign

0.014

T;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.19

T;T;.

MetaRNN

Benign

0.0059

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.31

.;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.99

N;N;N

REVEL

Benign

0.014

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.012

B;B;B

Vest4

0.12

MVP

0.18

MPC

0.071

ClinPred

0.0077

GERP RS

-8.8

Varity_R

0.071

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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