chr20-4857181-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005116.6(SLC23A2):​c.1744C>T​(p.Arg582Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,607,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SLC23A2
NM_005116.6 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.19224057).
BS2
High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC23A2NM_005116.6 linkuse as main transcriptc.1744C>T p.Arg582Trp missense_variant 17/17 ENST00000338244.6
SLC23A2NM_203327.2 linkuse as main transcriptc.1744C>T p.Arg582Trp missense_variant 17/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC23A2ENST00000338244.6 linkuse as main transcriptc.1744C>T p.Arg582Trp missense_variant 17/171 NM_005116.6 P1Q9UGH3-1
SLC23A2ENST00000379333.5 linkuse as main transcriptc.1744C>T p.Arg582Trp missense_variant 17/171 P1Q9UGH3-1

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
151992
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000967
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000897
AC:
22
AN:
245262
Hom.:
0
AF XY:
0.0000754
AC XY:
10
AN XY:
132622
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000586
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000164
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000116
AC:
169
AN:
1455484
Hom.:
0
Cov.:
31
AF XY:
0.000105
AC XY:
76
AN XY:
723456
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000451
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000376
Gnomad4 NFE exome
AF:
0.000148
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152110
Hom.:
0
Cov.:
32
AF XY:
0.000202
AC XY:
15
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.0000964
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000117
Hom.:
0
Bravo
AF:
0.000155
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000906
AC:
11
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsSep 22, 2023The c.1744C>T (p.R582W) alteration is located in exon 17 (coding exon 15) of the SLC23A2 gene. This alteration results from a C to T substitution at nucleotide position 1744, causing the arginine (R) at amino acid position 582 to be replaced by a tryptophan (W). 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
-0.28
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.61
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.94
.;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Uncertain
2.4
M;M
MutationTaster
Benign
0.94
D;D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.27
Sift
Benign
0.092
T;T
Sift4G
Uncertain
0.037
D;D
Polyphen
0.99
D;D
Vest4
0.42
MVP
0.13
MPC
1.2
ClinPred
0.66
D
GERP RS
-7.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.049
gMVP
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: rs139545711; hg19: chr20-4837827; API