NM_001199633.2:c.1091T>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001199633.2(SLC28A3):​c.1091T>A​(p.Met364Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SLC28A3
NM_001199633.2 missense

Scores

13
3
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.22
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.949

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC28A3NM_001199633.2 linkc.1091T>A p.Met364Lys missense_variant Exon 11 of 18 ENST00000376238.5 NP_001186562.1 Q9HAS3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC28A3ENST00000376238.5 linkc.1091T>A p.Met364Lys missense_variant Exon 11 of 18 1 NM_001199633.2 ENSP00000365413.4 Q9HAS3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461818
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727210
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.92
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T
Eigen
Pathogenic
0.98
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.083
D
MetaRNN
Pathogenic
0.95
D
MetaSVM
Uncertain
0.026
D
MutationAssessor
Pathogenic
4.5
H
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-5.7
D
REVEL
Pathogenic
0.77
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
0.99
D
Vest4
0.98
MutPred
0.82
Gain of ubiquitination at M364 (P = 0.0289);
MVP
0.26
MPC
0.86
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.98
gMVP
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs754723936; hg19: chr9-86905127; API