Genetic Variant NM_001136506.2:c.1286A>C (chr11-63081666-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001136506.2(SLC22A24):c.1286A>C(p.Glu429Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,393,136 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SLC22A24
NM_001136506.2 missense, splice_region

Scores

Splicing: ADA: 0.1392

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.1286A>C	p.Glu429Ala	missense splice_region	Exon 8 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.1286A>C	p.Glu429Ala	missense splice_region	Exon 8 of 10	ENSP00000480336.1	Q8N4F4-2
SLC22A24	ENST00000417740.5	TSL:5	c.1286A>C	p.Glu429Ala	missense splice_region	Exon 8 of 10	ENSP00000396586.1	Q8N4F4-3
SLC22A24	ENST00000908490.1		c.519-1669A>C		intron	N/A	ENSP00000578549.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000260

AC:

AN:

153696

AF XY:

0.0000245

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000674

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1393136

Hom.:

Cov.:

AF XY:

0.0000204

AC XY:

AN XY:

687572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31464

American (AMR)

AF:

0.00

AC:

AN:

35694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25140

East Asian (EAS)

AF:

0.00

AC:

AN:

35708

South Asian (SAS)

AF:

0.00

AC:

AN:

79118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.0000205

AC:

AN:

1073274

Other (OTH)

AF:

0.00

AC:

AN:

57776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

Benign

0.23

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.44

MetaSVM

Uncertain

0.0082

PhyloP100

2.0

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.2

REVEL

Uncertain

0.54

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.053

Polyphen

1.0

Vest4

0.20

MutPred

0.63

Gain of catalytic residue at E429 (P = 0.0841)

MVP

0.56

MPC

0.019

ClinPred

0.95

GERP RS

3.5

gMVP

0.24

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.14

dbscSNV1_RF

Benign

0.45

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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