Genetic Variant SLC22A24:p.Val460Ile (chr11-63081574-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001136506.2(SLC22A24):c.1378G>A(p.Val460Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,550,946 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

SLC22A24
NM_001136506.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.609

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046144754).

BP6

Variant 11-63081574-C-T is Benign according to our data. Variant chr11-63081574-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3443137.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A24	NM_001136506.2 link	c.1378G>A	p.Val460Ile	missense_variant	Exon 8 of 10	ENST00000612278.4	NP_001129978.2	Q8N4F4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A24	ENST00000612278.4 link	c.1378G>A	p.Val460Ile	missense_variant	Exon 8 of 10	5	NM_001136506.2	ENSP00000480336.1		Q8N4F4-2
SLC22A24	ENST00000417740.5 link	c.1378G>A	p.Val460Ile	missense_variant	Exon 8 of 10	5		ENSP00000396586.1		Q8N4F4-3

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000195

AC:

AN:

153818

Hom.:

AF XY:

0.000245

AC XY:

AN XY:

81604

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.0000810

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000966

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000336

Gnomad OTH exome

AF:

0.000694

GnomAD4 exome

AF:

0.000107

AC:

149

AN:

1398748

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

689940

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.00104

Gnomad4 FIN exome

AF:

0.0000406

Gnomad4 NFE exome

AF:

0.0000454

Gnomad4 OTH exome

AF:

0.000172

GnomAD4 genome

AF:

0.000131

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000823

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000405

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 05, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.093

DANN

Benign

0.15

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00053

LIST_S2

Benign

0.16

T;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.48

PROVEAN

Benign

0.43

N;.

REVEL

Benign

0.074

Sift

Benign

1.0

T;.

Sift4G

Benign

0.99

T;T

Polyphen

0.029

B;.

Vest4

0.079

MVP

0.10

MPC

0.0071

ClinPred

0.0037

GERP RS

-6.6

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over