chr11-63081574-C-T

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

17

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]

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
SLC22A24NM_001136506.2 linkc.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
SLC22A24ENST00000612278.4 linkc.1378G>A p.Val460Ile missense_variant Exon 8 of 10 5 NM_001136506.2 ENSP00000480336.1 Q8N4F4-2
SLC22A24ENST00000417740.5 linkc.1378G>A p.Val460Ile missense_variant Exon 8 of 10 5 ENSP00000396586.1 Q8N4F4-3

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152080
Hom.:
0
Cov.:
33
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:
30
AN:
153818
Hom.:
0
AF XY:
0.000245
AC XY:
20
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.:
1
Cov.:
31
AF XY:
0.000123
AC XY:
85
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:
20
AN:
152198
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
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.:
0
Bravo
AF:
0.0000982
ESP6500AA
AF:
0.000723
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000405
AC:
9
Asia WGS
AF:
0.00173
AC:
6
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
T
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
N
LIST_S2
Benign
0.16
T;T
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.046
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.48
T
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
T
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.

Other links and lift over

dbSNP: rs375541298; hg19: chr11-62849046; API