11-26673490-C-T

Variant summary

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

The NM_178498.4(SLC5A12):​c.1619G>A​(p.Arg540Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,611,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SLC5A12
NM_178498.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75
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]

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=0.22162175).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC5A12NM_178498.4 linkc.1619G>A p.Arg540Lys missense_variant Exon 14 of 15 ENST00000396005.8 NP_848593.2 Q1EHB4-1
SLC5A12XM_006718155.4 linkc.1286G>A p.Arg429Lys missense_variant Exon 14 of 15 XP_006718218.1
SLC5A12XM_011519920.3 linkc.1055G>A p.Arg352Lys missense_variant Exon 15 of 16 XP_011518222.1
SLC5A12XM_017017244.2 linkc.1055G>A p.Arg352Lys missense_variant Exon 15 of 16 XP_016872733.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC5A12ENST00000396005.8 linkc.1619G>A p.Arg540Lys missense_variant Exon 14 of 15 1 NM_178498.4 ENSP00000379326.3 Q1EHB4-1
SLC5A12ENST00000527405.5 linkn.*225G>A non_coding_transcript_exon_variant Exon 14 of 15 2 ENSP00000436011.1 G3V1E3
SLC5A12ENST00000527405.5 linkn.*225G>A 3_prime_UTR_variant Exon 14 of 15 2 ENSP00000436011.1 G3V1E3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152182
Hom.:
0
Cov.:
32
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000284
AC:
7
AN:
246704
Hom.:
0
AF XY:
0.0000224
AC XY:
3
AN XY:
133878
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000624
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000164
AC:
24
AN:
1459456
Hom.:
0
Cov.:
32
AF XY:
0.0000179
AC XY:
13
AN XY:
725930
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:
0.0000216
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152182
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000113
EpiCase
AF:
0.00
EpiControl
AF:
0.0000601

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 18, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1619G>A (p.R540K) alteration is located in exon 14 (coding exon 14) of the SLC5A12 gene. This alteration results from a G to A substitution at nucleotide position 1619, causing the arginine (R) at amino acid position 540 to be replaced by a lysine (K). 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
0.14
BayesDel_addAF
Benign
-0.063
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0056
T
Eigen
Benign
-0.19
Eigen_PC
Benign
0.043
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
1.5
L
PrimateAI
Benign
0.46
T
PROVEAN
Benign
0.58
N
REVEL
Uncertain
0.42
Sift
Benign
1.0
T
Sift4G
Benign
0.32
T
Polyphen
0.0010
B
Vest4
0.27
MutPred
0.51
Gain of methylation at R540 (P = 0.0189);
MVP
0.81
MPC
0.20
ClinPred
0.19
T
GERP RS
5.6
Varity_R
0.15
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
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.

Other links and lift over

dbSNP: rs1201897929; hg19: chr11-26695037; API