chr17-28491461-C-T

Variant summary

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

The NM_003984.4(SLC13A2):​c.599C>T​(p.Thr200Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 1,613,710 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 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

SLC13A2
NM_003984.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.116
Variant links:
Genes affected
SLC13A2 (HGNC:10917): (solute carrier family 13 member 2) The protein encoded by this gene is a sodium-coupled citrate transporter that is regulated by the chaperone activity of cyclophilin b. The encoded protein may play a role in the formation of kidney stones. [provided by RefSeq, Oct 2016]
RSKR (HGNC:26314): (ribosomal protein S6 kinase related) Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. [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=0.012827992).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC13A2NM_003984.4 linkuse as main transcriptc.599C>T p.Thr200Met missense_variant 5/12 ENST00000314669.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC13A2ENST00000314669.10 linkuse as main transcriptc.599C>T p.Thr200Met missense_variant 5/121 NM_003984.4 P1Q13183-1

Frequencies

GnomAD3 genomes
AF:
0.0000525
AC:
8
AN:
152250
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000963
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000120
AC:
30
AN:
250828
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00153
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000684
AC:
100
AN:
1461342
Hom.:
0
Cov.:
31
AF XY:
0.0000564
AC XY:
41
AN XY:
726998
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00196
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152368
Hom.:
0
Cov.:
33
AF XY:
0.0000671
AC XY:
5
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000965
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000425
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.000123
AC:
15
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
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 GeneticsFeb 15, 2023The c.746C>T (p.T249M) alteration is located in exon 5 (coding exon 5) of the SLC13A2 gene. This alteration results from a C to T substitution at nucleotide position 746, causing the threonine (T) at amino acid position 249 to be replaced by a methionine (M). 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
0.080
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
5.3
DANN
Benign
0.94
DEOGEN2
Benign
0.043
.;T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.41
T;T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.013
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.1
.;L;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.70
N;N;.
REVEL
Benign
0.098
Sift
Benign
0.066
T;T;.
Sift4G
Benign
0.10
T;T;T
Polyphen
0.016
.;B;.
Vest4
0.17
MVP
0.26
MPC
0.49
ClinPred
0.015
T
GERP RS
-0.74
Varity_R
0.019
gMVP
0.48

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: rs200761343; hg19: chr17-26818479; COSMIC: COSV58993492; API