11-63163951-A-G

Variant summary

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

The NM_199352.6(SLC22A25):ā€‹c.1517T>Cā€‹(p.Ile506Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

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

Consequence

SLC22A25
NM_199352.6 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.21
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 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
SLC22A25NM_199352.6 linkc.1517T>C p.Ile506Thr 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.1517T>C p.Ile506Thr missense_variant 12/121 NM_199352.6 ENSP00000307443.6 Q6T423

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461738
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
727172
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:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

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 GeneticsMar 23, 2023The c.1517T>C (p.I506T) alteration is located in exon 9 (coding exon 9) of the SLC22A25 gene. This alteration results from a T to C substitution at nucleotide position 1517, causing the isoleucine (I) at amino acid position 506 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
0.30
BayesDel_addAF
Benign
-0.0095
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.058
T
Eigen
Uncertain
0.39
Eigen_PC
Benign
0.20
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.0084
T
MetaRNN
Uncertain
0.73
D
MetaSVM
Uncertain
-0.022
T
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-4.0
D
REVEL
Uncertain
0.35
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.40
MutPred
0.67
Loss of stability (P = 0.0073);
MVP
0.48
MPC
0.090
ClinPred
0.95
D
GERP RS
4.7
Varity_R
0.42
gMVP
0.32

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: rs2087588950; hg19: chr11-62931423; API