11-63080927-C-T

Variant names:

• chr11-63080927-C-T
• NM_001136506.2:c.1591G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83

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]

ACMG classification

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
SLC22A24	NM_001136506.2	c.1591G>A	p.Glu531Lys	missense_variant	Exon 9 of 10	ENST00000612278.4	NP_001129978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A24	ENST00000612278.4	c.1591G>A	p.Glu531Lys	missense_variant	Exon 9 of 10	5	NM_001136506.2	ENSP00000480336.1
SLC22A24	ENST00000417740.5	c.1591G>A	p.Glu531Lys	missense_variant	Exon 9 of 10	5		ENSP00000396586.1

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

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;