11-63119003-G-T

Variant names:

• chr11-63119003-G-T
• rs1468108609
• NM_001136506.2:c.739C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136506.2(SLC22A24):​c.739C>A​(p.Leu247Ile) 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. 16/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L247F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A24 NM_001136506.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.39
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14926675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A24	NM_001136506.2	c.739C>A	p.Leu247Ile	missense_variant	Exon 4 of 10	ENST00000612278.4	NP_001129978.2
SLC22A24	NM_173586.3	c.739C>A	p.Leu247Ile	missense_variant	Exon 4 of 4		NP_775857.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A24	ENST00000612278.4	c.739C>A	p.Leu247Ile	missense_variant	Exon 4 of 10	5	NM_001136506.2	ENSP00000480336.1
SLC22A24	ENST00000417740.5	c.739C>A	p.Leu247Ile	missense_variant	Exon 4 of 10	5		ENSP00000396586.1
SLC22A24	ENST00000326192.5	c.739C>A	p.Leu247Ile	missense_variant	Exon 4 of 4	1		ENSP00000321549.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.0030
DANN	Benign	0.71
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.21	T;T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.98	T
PhyloP100		-3.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.28	N;.;N
REVEL	Benign	0.047
Sift	Benign	1.0	T;.;T
Sift4G	Benign	0.67	T;T;T
Polyphen		0.033	B;.;.
Vest4		0.17
MutPred		0.50		Gain of catalytic residue at L247 (P = 0.0465);Gain of catalytic residue at L247 (P = 0.0465);Gain of catalytic residue at L247 (P = 0.0465);
MVP		0.13
MPC		0.016
ClinPred		0.11	T
GERP RS		-0.82
gMVP		0.041
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs1468108609; hg19: chr11-62886475;