Variant 15-84895116-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004213.5(SLC28A1):c.454T>A(p.Phe152Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SLC28A1
NM_004213.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.752

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:

SLC28A1 (HGNC:):

SLC28A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06419811).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC28A1	NM_004213.5 linkuse as main transcript	c.454T>A	p.Phe152Ile	missense_variant	6/19	ENST00000394573.6	NP_004204.3	O00337-1B7Z3L5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC28A1	ENST00000394573.6 linkuse as main transcript	c.454T>A	p.Phe152Ile	missense_variant	6/19	1	NM_004213.5	ENSP00000378074.1	O00337-1
SLC28A1	ENST00000286749.3 linkuse as main transcript	c.454T>A	p.Phe152Ile	missense_variant	5/18	1		ENSP00000286749.3	O00337-1
SLC28A1	ENST00000338602.6 linkuse as main transcript	c.454T>A	p.Phe152Ile	missense_variant	6/7	1		ENSP00000341629.2	O00337-2
SLC28A1	ENST00000538177.5 linkuse as main transcript	c.454T>A	p.Phe152Ile	missense_variant	5/15	2		ENSP00000443752.1	B7Z3L6

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250426

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135532

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461560

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2024

The c.454T>A (p.F152I) alteration is located in exon 6 (coding exon 4) of the SLC28A1 gene. This alteration results from a T to A substitution at nucleotide position 454, causing the phenylalanine (F) at amino acid position 152 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.33

CADD

Benign

2.5

DANN

Benign

0.88

DEOGEN2

Benign

0.0044

.;T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.64

T;T;T;.

M_CAP

Benign

0.037

MetaRNN

Benign

0.064

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

L;.;L;L

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.050

N;N;N;N

REVEL

Benign

0.29

Sift

Benign

0.28

T;T;T;T

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.026

B;B;B;B

Vest4

0.30

MutPred

0.22

Loss of methylation at K153 (P = 0.0533);Loss of methylation at K153 (P = 0.0533);Loss of methylation at K153 (P = 0.0533);Loss of methylation at K153 (P = 0.0533);

MVP

0.14

MPC

0.12

ClinPred

0.057

GERP RS

-5.4

Varity_R

0.043

gMVP

0.21

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