chr6-43302689-G-A

Variant summary

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

The NM_153320.2(SLC22A7):​c.1311G>A​(p.Met437Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,608,248 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 (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

SLC22A7
NM_153320.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.75
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]
CRIP3 (HGNC:17751): (cysteine rich protein 3) Predicted to enable metal ion binding activity. Predicted to act upstream of or within T cell proliferation. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.032583773).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC22A7NM_153320.2 linkuse as main transcriptc.1311G>A p.Met437Ile missense_variant 9/11 ENST00000372585.10 NP_696961.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC22A7ENST00000372585.10 linkuse as main transcriptc.1311G>A p.Met437Ile missense_variant 9/115 NM_153320.2 ENSP00000361666 A1Q9Y694-1

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.000660
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000115
AC:
28
AN:
242802
Hom.:
0
AF XY:
0.0000993
AC XY:
13
AN XY:
130966
show subpopulations
Gnomad AFR exome
AF:
0.0000655
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:
0.000523
Gnomad NFE exome
AF:
0.000137
Gnomad OTH exome
AF:
0.000168
GnomAD4 exome
AF:
0.000156
AC:
227
AN:
1456070
Hom.:
0
Cov.:
31
AF XY:
0.000144
AC XY:
104
AN XY:
723680
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:
0.000715
Gnomad4 NFE exome
AF:
0.000165
Gnomad4 OTH exome
AF:
0.0000998
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000660
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000251
Hom.:
0
Bravo
AF:
0.0000831
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000107
AC:
13

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 GeneticsOct 16, 2023The c.1311G>A (p.M437I) alteration is located in exon 9 (coding exon 9) of the SLC22A7 gene. This alteration results from a G to A substitution at nucleotide position 1311, causing the methionine (M) at amino acid position 437 to be replaced by an isoleucine (I). 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
0.18
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
1.1
DANN
Benign
0.71
DEOGEN2
Benign
0.12
.;T;.;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.67
T;T;T;T
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.033
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.4
.;N;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
0.47
N;N;N;N
REVEL
Benign
0.10
Sift
Benign
0.67
T;T;T;T
Sift4G
Benign
0.56
T;T;T;T
Polyphen
0.0
B;B;B;.
Vest4
0.082
MutPred
0.57
.;Loss of catalytic residue at V433 (P = 0.0439);.;.;
MVP
0.23
MPC
0.35
ClinPred
0.028
T
GERP RS
-4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.047
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs144507531; hg19: chr6-43270427; API