11-63163912-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_199352.6(SLC22A25):ā€‹c.1556G>Cā€‹(p.Arg519Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,772 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

SLC22A25
NM_199352.6 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.551
Variant links:
Genes affected
SLC22A25 (HGNC:32935): (solute carrier family 22 member 25) Predicted to enable transmembrane transporter activity. Predicted to be involved in organic anion transport. Predicted to be integral component of membrane. [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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32687962).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC22A25NM_199352.6 linkc.1556G>C p.Arg519Thr missense_variant 12/12 ENST00000306494.11 NP_955384.3 Q6T423

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC22A25ENST00000306494.11 linkc.1556G>C p.Arg519Thr missense_variant 12/121 NM_199352.6 ENSP00000307443.6 Q6T423

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152078
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250918
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135582
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461694
Hom.:
0
Cov.:
29
AF XY:
0.00000413
AC XY:
3
AN XY:
727142
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:
0.0000562
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152078
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74274
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000821
Hom.:
0

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 GeneticsJan 20, 2023The c.1556G>C (p.R519T) alteration is located in exon 9 (coding exon 9) of the SLC22A25 gene. This alteration results from a G to C substitution at nucleotide position 1556, causing the arginine (R) at amino acid position 519 to be replaced by a threonine (T). 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
0.27
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.036
T
Eigen
Uncertain
0.24
Eigen_PC
Benign
0.10
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-0.50
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-4.3
D
REVEL
Benign
0.24
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.016
D
Polyphen
1.0
D
Vest4
0.29
MutPred
0.50
Gain of glycosylation at R519 (P = 0.0217);
MVP
0.41
MPC
0.052
ClinPred
0.96
D
GERP RS
2.8
Varity_R
0.16
gMVP
0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1171741106; hg19: chr11-62931384; API