6-3285097-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015482.2(SLC22A23):​c.1561A>T​(p.Ser521Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Consequence

SLC22A23
NM_015482.2 missense

Scores

1
13
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.07
Variant links:
Genes affected
SLC22A23 (HGNC:21106): (solute carrier family 22 member 23) SLC22A23 belongs to a large family of transmembrane proteins that function as uniporters, symporters, and antiporters to transport organic ions across cell membranes (Jacobsson et al., 2007 [PubMed 17714910]).[supplied by OMIM, Mar 2008]
PSMG4 (HGNC:21108): (proteasome assembly chaperone 4) Predicted to be involved in proteasome assembly. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC22A23NM_015482.2 linkuse as main transcriptc.1561A>T p.Ser521Cys missense_variant 8/10 ENST00000406686.8 NP_056297.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC22A23ENST00000406686.8 linkuse as main transcriptc.1561A>T p.Ser521Cys missense_variant 8/105 NM_015482.2 ENSP00000385028 P2A1A5C7-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
37
GnomAD4 genome
Cov.:
34

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 GeneticsFeb 02, 2024The c.1561A>T (p.S521C) alteration is located in exon 8 (coding exon 8) of the SLC22A23 gene. This alteration results from a A to T substitution at nucleotide position 1561, causing the serine (S) at amino acid position 521 to be replaced by a cysteine (C). 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
Uncertain
0.48
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
.;T;.;.;T;.
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.86
D;D;.;D;D;D
M_CAP
Uncertain
0.099
D
MetaRNN
Uncertain
0.64
D;D;D;D;D;D
MetaSVM
Benign
-0.35
T
MutationAssessor
Uncertain
2.3
.;M;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.9
N;N;N;N;N;N
REVEL
Uncertain
0.58
Sift
Benign
0.063
T;T;T;T;T;T
Sift4G
Uncertain
0.010
D;D;D;D;D;.
Polyphen
1.0
D;D;.;.;.;.
Vest4
0.68
MutPred
0.60
Loss of disorder (P = 8e-04);Loss of disorder (P = 8e-04);.;.;.;.;
MVP
0.77
MPC
1.0
ClinPred
0.92
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr6-3285331; API