Variant chr6-43299093-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_153320.2(SLC22A7):c.395C>T(p.Ser132Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00052 in 1,605,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 0 hom. )

Consequence

SLC22A7
NM_153320.2 missense, splice_region

Scores

Splicing: ADA: 0.0005217

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.368

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]

SLC22A7 links:

LOC124901319 (HGNC:):

LOC124901319 links:

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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=0.033052623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A7	NM_153320.2 linkuse as main transcript	c.395C>T	p.Ser132Phe	missense_variant, splice_region_variant	2/11	ENST00000372585.10	NP_696961.2
LOC124901319	XR_007059582.1 linkuse as main transcript	n.904G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A7	ENST00000372585.10 linkuse as main transcript	c.395C>T	p.Ser132Phe	missense_variant, splice_region_variant	2/11	5	NM_153320.2	ENSP00000361666	A1	Q9Y694-1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000522

AC:

127

AN:

243482

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

131760

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000596

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.000544

AC:

791

AN:

1452928

Hom.:

Cov.:

AF XY:

0.000499

AC XY:

360

AN XY:

721864

show subpopulations

Gnomad4 AFR exome

AF:

0.000241

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.000674

Gnomad4 OTH exome

AF:

0.000450

GnomAD4 genome

AF:

0.000283

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000519

Hom.:

Bravo

AF:

0.000261

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000675

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000890

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 submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.395C>T (p.S132F) alteration is located in exon 2 (coding exon 2) of the SLC22A7 gene. This alteration results from a C to T substitution at nucleotide position 395, causing the serine (S) at amino acid position 132 to be replaced by a phenylalanine (F). 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

0.27

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.41

CADD

Benign

9.7

DANN

Benign

0.72

DEOGEN2

Benign

0.0021

T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

0.060

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0040

D;T

Sift4G

Uncertain

0.017

D;T

Vest4

0.23

MVP

0.53

MPC

0.36

ClinPred

0.032

GERP RS

2.9

Varity_R

0.034

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00052

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over