6-43298383-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153320.2(SLC22A7):ā€‹c.25C>Gā€‹(p.Gln9Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000068 ( 0 hom. )

Consequence

SLC22A7
NM_153320.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0620
Variant links:
Genes affected
SLC22A7 (HGNC:10971): (solute carrier family 22 member 7) The protein encoded by this gene is involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.031591028).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC22A7NM_153320.2 linkuse as main transcriptc.25C>G p.Gln9Glu missense_variant 1/11 ENST00000372585.10 NP_696961.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC22A7ENST00000372585.10 linkuse as main transcriptc.25C>G p.Gln9Glu missense_variant 1/115 NM_153320.2 ENSP00000361666 A1Q9Y694-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152236
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00000805
AC:
2
AN:
248372
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134554
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000685
AC:
10
AN:
1460446
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726314
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152236
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000566
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 07, 2023The c.25C>G (p.Q9E) alteration is located in exon 1 (coding exon 1) of the SLC22A7 gene. This alteration results from a C to G substitution at nucleotide position 25, causing the glutamine (Q) at amino acid position 9 to be replaced by a glutamic acid (E). 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
0.072
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
5.8
DANN
Benign
0.58
DEOGEN2
Benign
0.0047
T;.;T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.083
N
LIST_S2
Benign
0.70
T;T;T;T
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.032
T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-0.17
.;N;N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
0.61
N;N;N;N
REVEL
Benign
0.062
Sift
Benign
0.98
T;T;T;T
Sift4G
Benign
0.69
T;T;T;T
Polyphen
0.0
.;B;B;B
Vest4
0.12, 0.11, 0.15
MutPred
0.44
Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);
MVP
0.19
MPC
0.34
ClinPred
0.036
T
GERP RS
-1.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.040
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs770878980; hg19: chr6-43266121; API