Variant 15-84890532-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000394573.6(SLC28A1):c.275C>T(p.Thr92Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,455,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SLC28A1
ENST00000394573.6 missense, splice_region

Scores

Splicing: ADA: 0.4799

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.53

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42111862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC28A1	NM_004213.5 linkuse as main transcript	c.275C>T	p.Thr92Ile	missense_variant, splice_region_variant	5/19	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.275C>T	p.Thr92Ile	missense_variant, splice_region_variant	5/19	1	NM_004213.5	ENSP00000378074	P1	O00337-1
SLC28A1	ENST00000286749.3 linkuse as main transcript	c.275C>T	p.Thr92Ile	missense_variant, splice_region_variant	4/18	1		ENSP00000286749	P1	O00337-1
SLC28A1	ENST00000338602.6 linkuse as main transcript	c.275C>T	p.Thr92Ile	missense_variant, splice_region_variant	5/7	1		ENSP00000341629		O00337-2
SLC28A1	ENST00000538177.5 linkuse as main transcript	c.275C>T	p.Thr92Ile	missense_variant, splice_region_variant	4/15	2		ENSP00000443752

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

244404

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132458

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1455324

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

723952

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000451

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Apr 18, 2024

The c.275C>T (p.T92I) alteration is located in exon 5 (coding exon 3) of the SLC28A1 gene. This alteration results from a C to T substitution at nucleotide position 275, causing the threonine (T) at amino acid position 92 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

0.11

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0053

.;T;T;T

Eigen

Benign

0.084

Eigen_PC

Benign

0.078

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.69

T;T;T;.

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.42

T;T;T;T

MetaSVM

Uncertain

0.28

MutationAssessor

Uncertain

2.4

M;.;M;M

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Uncertain

0.51

Sift

Benign

0.48

T;T;T;T

Sift4G

Benign

0.19

T;T;T;T

Polyphen

1.0

D;P;B;B

Vest4

0.68

MutPred

0.36

Loss of catalytic residue at T92 (P = 0.152);Loss of catalytic residue at T92 (P = 0.152);Loss of catalytic residue at T92 (P = 0.152);Loss of catalytic residue at T92 (P = 0.152);

MVP

0.90

MPC

0.22

ClinPred

0.33

GERP RS

4.3

Varity_R

0.096

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.48

dbscSNV1_RF

Benign

0.43

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