chr11-63080927-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/19 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29568043).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136506.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A24	NM_001136506.2	MANE Select	c.1591G>A	p.Glu531Lys	missense	Exon 9 of 10	NP_001129978.2	Q8N4F4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A24	ENST00000612278.4	TSL:5 MANE Select	c.1591G>A	p.Glu531Lys	missense	Exon 9 of 10	ENSP00000480336.1	Q8N4F4-2
	SLC22A24	ENST00000417740.5	TSL:5	c.1591G>A	p.Glu531Lys	missense	Exon 9 of 10	ENSP00000396586.1	Q8N4F4-3
	SLC22A24	ENST00000908490.1		c.519-930G>A		intron	N/A	ENSP00000578549.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.48	T
PhyloP100		1.8
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.25
Sift	Benign	0.19	T
Sift4G	Benign	0.15	T
Polyphen		0.30	B
Vest4		0.17
MutPred		0.58		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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr11-62848399;