9-84286062-T-G

Variant summary

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

The NM_001199633.2(SLC28A3):ā€‹c.1330A>Cā€‹(p.Ile444Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

SLC28A3
NM_001199633.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.82
Variant links:
Genes affected
SLC28A3 (HGNC:16484): (solute carrier family 28 member 3) Nucleoside transporters, such as SLC28A3, regulate multiple cellular processes, including neurotransmission, vascular tone, adenosine concentration in the vicinity of cell surface receptors, and transport and metabolism of nucleoside drugs. SLC28A3 shows broad specificity for pyrimidine and purine nucleosides (Ritzel et al., 2001 [PubMed 11032837]).[supplied by OMIM, Mar 2008]
SLC28A3-AS1 (HGNC:55460): (SLC28A3 regulatory antisense RNA 1)

Genome browser will be placed here

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=0.25554323).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC28A3NM_001199633.2 linkc.1330A>C p.Ile444Leu missense_variant 13/18 ENST00000376238.5 NP_001186562.1 Q9HAS3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC28A3ENST00000376238.5 linkc.1330A>C p.Ile444Leu missense_variant 13/181 NM_001199633.2 ENSP00000365413.4 Q9HAS3-1
SLC28A3-AS1ENST00000419815.1 linkn.182-3878T>G intron_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
251046
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135656
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461802
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727198
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 GeneticsAug 26, 2024The c.1330A>C (p.I444L) alteration is located in exon 14 (coding exon 13) of the SLC28A3 gene. This alteration results from a A to C substitution at nucleotide position 1330, causing the isoleucine (I) at amino acid position 444 to be replaced by a leucine (L). 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
0.16
BayesDel_addAF
Benign
-0.093
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.012
T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.090
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.26
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.88
L
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.17
Sift
Uncertain
0.0060
D
Sift4G
Benign
0.081
T
Polyphen
0.26
B
Vest4
0.49
MutPred
0.53
Gain of disorder (P = 0.1309);
MVP
0.030
MPC
0.29
ClinPred
0.31
T
GERP RS
4.7
Varity_R
0.82
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
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: rs755511024; hg19: chr9-86900977; API