Genetic Variant SLC22A24:p.Gly502Arg (chr11-63081014-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001136506.2(SLC22A24):c.1504G>A(p.Gly502Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000286 in 1,399,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SLC22A24
NM_001136506.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.10

Publications

0 publications found

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]

SLC22A24 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.959

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.1504G>A	p.Gly502Arg	missense	Exon 9 of 10	NP_001129978.2	Q8N4F4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC22A24	ENST00000612278.4	TSL:5 MANE Select	c.1504G>A	p.Gly502Arg	missense	Exon 9 of 10	ENSP00000480336.1	Q8N4F4-2
SLC22A24	ENST00000417740.5	TSL:5	c.1504G>A	p.Gly502Arg	missense	Exon 9 of 10	ENSP00000396586.1	Q8N4F4-3
SLC22A24	ENST00000908490.1		c.519-1017G>A		intron	N/A	ENSP00000578549.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000193

AC:

AN:

155182

AF XY:

0.0000243

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1399536

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

690332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.000112

AC:

AN:

35706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.00

AC:

AN:

35740

South Asian (SAS)

AF:

0.00

AC:

AN:

79238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079086

Other (OTH)

AF:

0.00

AC:

AN:

58034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Pathogenic

1.0

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Benign

0.39

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.029

MetaRNN

Pathogenic

0.96

MetaSVM

Uncertain

0.35

PhyloP100

4.1

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-7.0

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.60

MutPred

0.84

Loss of catalytic residue at V503 (P = 0.0316)

MVP

0.73

MPC

0.034

ClinPred

0.96

GERP RS

3.5

gMVP

0.79

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over