20-4869993-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_005116.6(SLC23A2):c.1163T>A(p.Val388Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,750 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: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SLC23A2
NM_005116.6 missense
NM_005116.6 missense
Scores
9
6
4
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
SLC23A2 (HGNC:10973): (solute carrier family 23 member 2) The absorption of vitamin C into the body and its distribution to organs requires two sodium-dependent vitamin C transporters. This gene encodes one of the two required transporters and the encoded protein accounts for tissue-specific uptake of vitamin C. Previously, this gene had an official symbol of SLC23A1. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.908
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC23A2 | NM_005116.6 | c.1163T>A | p.Val388Asp | missense_variant | 12/17 | ENST00000338244.6 | NP_005107.4 | |
SLC23A2 | NM_203327.2 | c.1163T>A | p.Val388Asp | missense_variant | 12/17 | NP_976072.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC23A2 | ENST00000338244.6 | c.1163T>A | p.Val388Asp | missense_variant | 12/17 | 1 | NM_005116.6 | ENSP00000344322 | P1 | |
SLC23A2 | ENST00000379333.5 | c.1163T>A | p.Val388Asp | missense_variant | 12/17 | 1 | ENSP00000368637 | P1 | ||
SLC23A2 | ENST00000468355.5 | n.1529T>A | non_coding_transcript_exon_variant | 12/12 | 1 | |||||
SLC23A2 | ENST00000423430.1 | c.434T>A | p.Val145Asp | missense_variant | 4/8 | 5 | ENSP00000396364 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152106Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461644Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727122
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152106Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74310
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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 09, 2024 | The c.1163T>A (p.V388D) alteration is located in exon 12 (coding exon 10) of the SLC23A2 gene. This alteration results from a T to A substitution at nucleotide position 1163, causing the valine (V) at amino acid position 388 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of glycosylation at S385 (P = 0.217);Loss of glycosylation at S385 (P = 0.217);
MVP
MPC
2.4
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at