15-45264680-G-C

Variant summary

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

The NM_004212.4(SLC28A2):​c.614G>C​(p.Gly205Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SLC28A2
NM_004212.4 missense

Scores

6
7
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.56
Variant links:
Genes affected
SLC28A2 (HGNC:11002): (solute carrier family 28 member 2) Enables neurotransmitter transmembrane transporter activity and nucleoside transmembrane transporter activity. Involved in several processes, including nucleoside transport; purine nucleobase transmembrane transport; and pyrimidine-containing compound transmembrane transport. Predicted to be located in membrane. Predicted to be part of brush border membrane; coated vesicle; and vesicle membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
SLC28A2-AS1 (HGNC:55417): (SLC28A2 antisense RNA 1)

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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, 0.948

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC28A2NM_004212.4 linkc.614G>C p.Gly205Ala missense_variant Exon 7 of 18 ENST00000347644.8 NP_004203.2 O43868Q2M2A7Q53H72
SLC28A2-AS1NR_120335.1 linkn.27-8682C>G intron_variant Intron 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC28A2ENST00000347644.8 linkc.614G>C p.Gly205Ala missense_variant Exon 7 of 18 1 NM_004212.4 ENSP00000315006.4 O43868

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460684
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726762
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
26
DANN
Benign
0.95
DEOGEN2
Benign
0.14
T;.
Eigen
Pathogenic
0.91
Eigen_PC
Pathogenic
0.90
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.96
D;T
M_CAP
Benign
0.022
T
MetaRNN
Pathogenic
0.95
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-5.7
D;D
REVEL
Uncertain
0.64
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.030
D;D
Polyphen
1.0
D;.
Vest4
0.81
MutPred
0.83
Loss of glycosylation at S204 (P = 0.0429);.;
MVP
0.47
MPC
0.30
ClinPred
0.99
D
GERP RS
6.2
Varity_R
0.89
gMVP
0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-45556878; API