chr6-43298374-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153320.2(SLC22A7):ā€‹c.16C>Gā€‹(p.Leu6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

SLC22A7
NM_153320.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0430
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13540742).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC22A7NM_153320.2 linkuse as main transcriptc.16C>G p.Leu6Val 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.16C>G p.Leu6Val missense_variant 1/115 NM_153320.2 ENSP00000361666 A1Q9Y694-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000404
AC:
1
AN:
247610
Hom.:
0
AF XY:
0.00000745
AC XY:
1
AN XY:
134224
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000550
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1459552
Hom.:
0
Cov.:
31
AF XY:
0.00000276
AC XY:
2
AN XY:
725834
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 GeneticsApr 13, 2022The c.16C>G (p.L6V) 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 16, causing the leucine (L) at amino acid position 6 to be replaced by a valine (V). 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
-0.26
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
16
DANN
Benign
0.76
DEOGEN2
Benign
0.030
T;.;T;.
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.41
N
LIST_S2
Benign
0.73
T;T;T;T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.91
.;L;L;L
MutationTaster
Benign
0.52
D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.96
N;N;N;N
REVEL
Benign
0.058
Sift
Benign
0.16
T;T;T;T
Sift4G
Benign
0.21
T;T;T;T
Polyphen
0.032, 0.019
.;B;B;B
Vest4
0.26, 0.26, 0.29
MutPred
0.60
Gain of disorder (P = 0.2331);Gain of disorder (P = 0.2331);Gain of disorder (P = 0.2331);Gain of disorder (P = 0.2331);
MVP
0.34
MPC
0.39
ClinPred
0.042
T
GERP RS
2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.071
gMVP
0.52

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: rs1196182957; hg19: chr6-43266112; API