11-26681166-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_178498.4(SLC5A12):​c.1364G>A​(p.Gly455Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G455V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC5A12
NM_178498.4 missense

Scores

13
4
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.26
Variant links:
Genes affected
SLC5A12 (HGNC:28750): (solute carrier family 5 member 12) Normal blood lactate is maintained at about 1.5 mM, and little filtered lactate is excreted in urine. Reabsorption of lactate is mediated by the low-affinity Na(+)-coupled lactate transporter SLC5A12 in the initial part of the proximal tubule and by the high-affinity Na(+)-coupled lactate transporter SLC5A8 (MIM 608044) in the distal proximal tubule (Gopal et al., 2007 [PubMed 17692818]).[supplied by OMIM, Dec 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC5A12NM_178498.4 linkc.1364G>A p.Gly455Glu missense_variant Exon 12 of 15 ENST00000396005.8 NP_848593.2 Q1EHB4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC5A12ENST00000396005.8 linkc.1364G>A p.Gly455Glu missense_variant Exon 12 of 15 1 NM_178498.4 ENSP00000379326.3 Q1EHB4-1
SLC5A12ENST00000527405.5 linkn.804G>A non_coding_transcript_exon_variant Exon 12 of 15 2 ENSP00000436011.1 G3V1E3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Pathogenic
0.45
D
BayesDel_noAF
Pathogenic
0.40
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.40
T
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.97
D
M_CAP
Pathogenic
0.32
D
MetaRNN
Pathogenic
0.93
D
MetaSVM
Pathogenic
0.82
D
MutationAssessor
Pathogenic
3.9
H
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-7.6
D
REVEL
Pathogenic
0.86
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.97
MutPred
0.67
Gain of catalytic residue at G455 (P = 0.0562);
MVP
0.95
MPC
0.87
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.91
gMVP
0.97

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs1329523764; hg19: chr11-26702713; API