Variant 15-84895110-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000394573.6(SLC28A1):c.448C>A(p.Leu150Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,864 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 1 hom. )

Consequence

SLC28A1
ENST00000394573.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.106

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08380929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC28A1	NM_004213.5 linkuse as main transcript	c.448C>A	p.Leu150Ile	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.448C>A	p.Leu150Ile	missense_variant	6/19	1	NM_004213.5	ENSP00000378074	P1	O00337-1
SLC28A1	ENST00000286749.3 linkuse as main transcript	c.448C>A	p.Leu150Ile	missense_variant	5/18	1		ENSP00000286749	P1	O00337-1
SLC28A1	ENST00000338602.6 linkuse as main transcript	c.448C>A	p.Leu150Ile	missense_variant	6/7	1		ENSP00000341629		O00337-2
SLC28A1	ENST00000538177.5 linkuse as main transcript	c.448C>A	p.Leu150Ile	missense_variant	5/15	2		ENSP00000443752

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

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:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250554

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135574

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.000116

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:

0.00000884

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461636

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000313

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:

0.00

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000223

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000472

ExAC

AF:

0.0000330

AC:

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 13, 2021

The c.448C>A (p.L150I) alteration is located in exon 6 (coding exon 4) of the SLC28A1 gene. This alteration results from a C to A substitution at nucleotide position 448, causing the leucine (L) at amino acid position 150 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

0.087

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.37

CADD

Benign

1.2

DANN

Benign

0.87

DEOGEN2

Benign

0.018

.;T;T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.68

T;T;T;.

M_CAP

Benign

0.017

MetaRNN

Benign

0.084

T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Pathogenic

3.0

M;.;M;M

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.98

N;N;N;N

REVEL

Benign

0.083

Sift

Uncertain

0.026

D;T;T;T

Sift4G

Uncertain

0.046

D;T;T;T

Polyphen

0.99

D;P;B;B

Vest4

0.14

MutPred

0.28

Gain of methylation at K153 (P = 0.0651);Gain of methylation at K153 (P = 0.0651);Gain of methylation at K153 (P = 0.0651);Gain of methylation at K153 (P = 0.0651);

MVP

0.31

MPC

0.084

ClinPred

0.036

GERP RS

0.40

Varity_R

0.049

gMVP

0.066

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