Genetic Variant SLC22A24:p.Leu247Phe (chr11-63119003-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001136506.2(SLC22A24):c.739C>T(p.Leu247Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000838 in 1,551,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

SLC22A24
NM_001136506.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.39

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3342763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A24	NM_001136506.2 link	c.739C>T	p.Leu247Phe	missense_variant	Exon 4 of 10	ENST00000612278.4	NP_001129978.2	Q8N4F4-2
SLC22A24	NM_173586.3 link	c.739C>T	p.Leu247Phe	missense_variant	Exon 4 of 4		NP_775857.2	Q8N4F4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC22A24	ENST00000612278.4 link	c.739C>T	p.Leu247Phe	missense_variant	Exon 4 of 10	5	NM_001136506.2	ENSP00000480336.1	Q8N4F4-2
SLC22A24	ENST00000417740.5 link	c.739C>T	p.Leu247Phe	missense_variant	Exon 4 of 10	5		ENSP00000396586.1	Q8N4F4-3
SLC22A24	ENST00000326192.5 link	c.739C>T	p.Leu247Phe	missense_variant	Exon 4 of 4	1		ENSP00000321549.5	Q8N4F4-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000128

AC:

AN:

156568

AF XY:

0.0000121

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:

0.0000594

Gnomad NFE exome

AF:

0.0000165

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000500

AC:

AN:

1399424

Hom.:

Cov.:

AF XY:

0.00000724

AC XY:

AN XY:

690220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31600

American (AMR)

AF:

0.00

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35734

South Asian (SAS)

AF:

0.00

AC:

AN:

79230

European-Finnish (FIN)

AF:

0.0000203

AC:

AN:

49324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00000463

AC:

AN:

1078918

Other (OTH)

AF:

0.00

AC:

AN:

58040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

AF:

0.0000394

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 07, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.739C>T (p.L247F) alteration is located in exon 4 (coding exon 4) of the SLC22A24 gene. This alteration results from a C to T substitution at nucleotide position 739, causing the leucine (L) at amino acid position 247 to be replaced by a phenylalanine (F). 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

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.017

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.20

T;T;.

M_CAP

Benign

0.023

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.70

PhyloP100

-3.4

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.1

N;.;N

REVEL

Benign

0.17

Sift

Uncertain

0.017

D;.;T

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.98

D;.;.

Vest4

0.15

MutPred

0.58

Gain of catalytic residue at L247 (P = 0.0641);Gain of catalytic residue at L247 (P = 0.0641);Gain of catalytic residue at L247 (P = 0.0641);

MVP

0.42

MPC

0.0086

ClinPred

0.088

GERP RS

-0.82

gMVP

0.14

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over