11-63080927-C-T

Variant summary

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

The NM_001136506.2(SLC22A24):​c.1591G>A​(p.Glu531Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SLC22A24
NM_001136506.2 missense

Scores

1
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83
Variant links:
Genes affected
SLC22A24 (HGNC:28542): (solute carrier family 22 member 24) SLC22A24 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]

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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=0.29568043).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC22A24NM_001136506.2 linkc.1591G>A p.Glu531Lys missense_variant Exon 9 of 10 ENST00000612278.4 NP_001129978.2 Q8N4F4-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC22A24ENST00000612278.4 linkc.1591G>A p.Glu531Lys missense_variant Exon 9 of 10 5 NM_001136506.2 ENSP00000480336.1 Q8N4F4-2
SLC22A24ENST00000417740.5 linkc.1591G>A p.Glu531Lys missense_variant Exon 9 of 10 5 ENSP00000396586.1 Q8N4F4-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1591G>A (p.E531K) alteration is located in exon 9 (coding exon 9) of the SLC22A24 gene. This alteration results from a G to A substitution at nucleotide position 1591, causing the glutamic acid (E) at amino acid position 531 to be replaced by a lysine (K). 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
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
16
DANN
Uncertain
1.0
Eigen
Benign
0.064
Eigen_PC
Benign
0.11
FATHMM_MKL
Benign
0.63
D
LIST_S2
Benign
0.70
T;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-0.48
T
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-2.4
N;.
REVEL
Benign
0.25
Sift
Benign
0.19
T;.
Sift4G
Benign
0.15
T;T
Polyphen
0.30
B;.
Vest4
0.17
MutPred
0.58
Gain of methylation at E531 (P = 0.0037);Gain of methylation at E531 (P = 0.0037);
MVP
0.48
MPC
0.034
ClinPred
0.91
D
GERP RS
3.5
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: chr11-62848399; API