rs376024540

Variant summary

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

The ENST00000433363.7(SLC13A5):​c.190G>A​(p.Val64Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,792 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: 6.8e-7 ( 0 hom. )

Consequence

SLC13A5
ENST00000433363.7 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80
Variant links:
Genes affected
SLC13A5 (HGNC:23089): (solute carrier family 13 member 5) This gene encodes a protein belonging to the solute carrier family 13 group of proteins. This family member is a sodium-dependent citrate cotransporter that may regulate metabolic processes. Mutations in this gene cause early infantile epileptic encephalopathy 25. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

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=0.055118233).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC13A5NM_177550.5 linkuse as main transcriptc.190G>A p.Val64Ile missense_variant 2/12 ENST00000433363.7 NP_808218.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC13A5ENST00000433363.7 linkuse as main transcriptc.190G>A p.Val64Ile missense_variant 2/121 NM_177550.5 ENSP00000406220 P1Q86YT5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251356
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135866
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461792
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 25 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 01, 2021This sequence change replaces valine with isoleucine at codon 64 of the SLC13A5 protein (p.Val64Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs376024540, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with SLC13A5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
17
DANN
Benign
0.95
DEOGEN2
Benign
0.077
T;.;.
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.24
N
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.055
T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.26
N;N;N
MutationTaster
Benign
1.0
D;N;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.33
N;N;.
REVEL
Benign
0.13
Sift
Benign
0.98
T;T;.
Sift4G
Benign
1.0
T;T;T
Polyphen
0.025
B;.;.
Vest4
0.11
MVP
0.13
MPC
0.25
ClinPred
0.095
T
GERP RS
5.4
Varity_R
0.16
gMVP
0.31

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: rs376024540; hg19: chr17-6610388; API