6-43299946-G-A

Variant summary

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

The NM_153320.2(SLC22A7):​c.707G>A​(p.Ser236Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,894 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SLC22A7
NM_153320.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.343
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 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=0.12184191).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC22A7NM_153320.2 linkuse as main transcriptc.707G>A p.Ser236Asn missense_variant 5/11 ENST00000372585.10 NP_696961.2
LOC124901319XR_007059582.1 linkuse as main transcriptn.181-130C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC22A7ENST00000372585.10 linkuse as main transcriptc.707G>A p.Ser236Asn missense_variant 5/115 NM_153320.2 ENSP00000361666 A1Q9Y694-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461894
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727248
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsJun 30, 2022The c.707G>A (p.S236N) alteration is located in exon 5 (coding exon 5) of the SLC22A7 gene. This alteration results from a G to A substitution at nucleotide position 707, causing the serine (S) at amino acid position 236 to be replaced by an asparagine (N). 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
Uncertain
0.54
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
19
DANN
Benign
0.78
DEOGEN2
Benign
0.17
.;.;T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.090
N
LIST_S2
Benign
0.78
T;T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.12
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;.;L;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-1.2
N;N;N;N
REVEL
Benign
0.050
Sift
Benign
0.23
T;T;T;T
Sift4G
Benign
0.50
T;T;T;T
Polyphen
0.26, 0.31
.;B;B;B
Vest4
0.44, 0.44, 0.46
MutPred
0.40
.;.;Gain of helix (P = 0.132);.;
MVP
0.38
MPC
0.74
ClinPred
0.31
T
GERP RS
1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.051
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-43267684; COSMIC: COSV99055825; COSMIC: COSV99055825; API