chr15-84894964-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004213.5(SLC28A1):​c.302C>T​(p.Ala101Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC28A1
NM_004213.5 missense

Scores

8
7
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC28A1NM_004213.5 linkuse as main transcriptc.302C>T p.Ala101Val missense_variant 6/19 ENST00000394573.6 NP_004204.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC28A1ENST00000394573.6 linkuse as main transcriptc.302C>T p.Ala101Val missense_variant 6/191 NM_004213.5 ENSP00000378074 P1O00337-1
SLC28A1ENST00000286749.3 linkuse as main transcriptc.302C>T p.Ala101Val missense_variant 5/181 ENSP00000286749 P1O00337-1
SLC28A1ENST00000338602.6 linkuse as main transcriptc.302C>T p.Ala101Val missense_variant 6/71 ENSP00000341629 O00337-2
SLC28A1ENST00000538177.5 linkuse as main transcriptc.302C>T p.Ala101Val missense_variant 5/152 ENSP00000443752

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461878
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
EpiCase
AF:
0.0000545
EpiControl
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 submitterclinical testingAmbry GeneticsDec 07, 2023The c.302C>T (p.A101V) alteration is located in exon 6 (coding exon 4) of the SLC28A1 gene. This alteration results from a C to T substitution at nucleotide position 302, causing the alanine (A) at amino acid position 101 to be replaced by a valine (V). 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
0.26
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.28
.;T;T;T
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.88
D;D;D;.
M_CAP
Pathogenic
0.29
D
MetaRNN
Pathogenic
0.82
D;D;D;D
MetaSVM
Uncertain
0.63
D
MutationAssessor
Pathogenic
3.4
M;.;M;M
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-3.9
D;D;D;D
REVEL
Uncertain
0.64
Sift
Uncertain
0.0020
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.81
MutPred
0.40
Gain of catalytic residue at F106 (P = 0.4572);Gain of catalytic residue at F106 (P = 0.4572);Gain of catalytic residue at F106 (P = 0.4572);Gain of catalytic residue at F106 (P = 0.4572);
MVP
0.87
MPC
0.44
ClinPred
1.0
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.57
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1030637478; hg19: chr15-85438195; API