6-160243653-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003058.4(SLC22A2):​c.1198C>T​(p.Arg400Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000835 in 1,613,962 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0043 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00048 ( 4 hom. )

Consequence

SLC22A2
NM_003058.4 missense

Scores

6
7
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.77
Variant links:
Genes affected
SLC22A2 (HGNC:10966): (solute carrier family 22 member 2) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. It is found primarily in the kidney, where it may mediate the first step in cation reabsorption. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.021221578).
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC22A2NM_003058.4 linkuse as main transcriptc.1198C>T p.Arg400Cys missense_variant 7/11 ENST00000366953.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC22A2ENST00000366953.8 linkuse as main transcriptc.1198C>T p.Arg400Cys missense_variant 7/111 NM_003058.4 P1O15244-1
SLC22A2ENST00000486916.5 linkuse as main transcriptn.237C>T non_coding_transcript_exon_variant 2/63
SLC22A2ENST00000491092.1 linkuse as main transcriptn.1095C>T non_coding_transcript_exon_variant 6/105

Frequencies

GnomAD3 genomes
AF:
0.00428
AC:
650
AN:
152046
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0146
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00150
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00123
AC:
309
AN:
251316
Hom.:
4
AF XY:
0.00102
AC XY:
139
AN XY:
135818
show subpopulations
Gnomad AFR exome
AF:
0.0159
Gnomad AMR exome
AF:
0.000896
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000114
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000475
AC:
695
AN:
1461796
Hom.:
4
Cov.:
31
AF XY:
0.000415
AC XY:
302
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.0148
Gnomad4 AMR exome
AF:
0.000962
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000927
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000558
Gnomad4 OTH exome
AF:
0.00113
GnomAD4 genome
AF:
0.00429
AC:
653
AN:
152166
Hom.:
2
Cov.:
32
AF XY:
0.00415
AC XY:
309
AN XY:
74392
show subpopulations
Gnomad4 AFR
AF:
0.0146
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.000607
Hom.:
1
Bravo
AF:
0.00488
ESP6500AA
AF:
0.0148
AC:
65
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00146
AC:
177
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.77
D
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D
MetaRNN
Benign
0.021
T
MetaSVM
Uncertain
0.0010
D
MutationAssessor
Pathogenic
3.5
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.57
T
PROVEAN
Pathogenic
-7.3
D
REVEL
Uncertain
0.40
Sift
Uncertain
0.027
D
Sift4G
Uncertain
0.020
D
Polyphen
0.99
D
Vest4
0.93
MVP
0.82
MPC
0.30
ClinPred
0.088
T
GERP RS
5.5
Varity_R
0.73
gMVP
0.83

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

LitVar

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

Other links and lift over

dbSNP: rs8177516; hg19: chr6-160664685; API