11-26686492-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178498.4(SLC5A12):​c.1206G>T​(p.Met402Ile) 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 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC5A12
NM_178498.4 missense

Scores

10
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC5A12NM_178498.4 linkc.1206G>T p.Met402Ile missense_variant Exon 10 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.1206G>T p.Met402Ile missense_variant Exon 10 of 15 1 NM_178498.4 ENSP00000379326.3 Q1EHB4-1
SLC5A12ENST00000527405.5 linkn.646G>T non_coding_transcript_exon_variant Exon 10 of 15 2 ENSP00000436011.1 G3V1E3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249438
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135324
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
1461738
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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
ExAC
AF:
0.00000827
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 29, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1206G>T (p.M402I) alteration is located in exon 10 (coding exon 10) of the SLC5A12 gene. This alteration results from a G to T substitution at nucleotide position 1206, causing the methionine (M) at amino acid position 402 to be replaced by an isoleucine (I). 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
Uncertain
0.55
BayesDel_addAF
Benign
-0.089
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.033
T
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.45
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.76
T
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.45
T
MetaSVM
Uncertain
-0.044
T
MutationAssessor
Benign
1.1
L
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-2.4
N
REVEL
Uncertain
0.38
Sift
Uncertain
0.010
D
Sift4G
Uncertain
0.058
T
Polyphen
0.13
B
Vest4
0.47
MutPred
0.63
Gain of helix (P = 0.0854);
MVP
0.61
MPC
0.22
ClinPred
0.39
T
GERP RS
2.6
Varity_R
0.37
gMVP
0.47

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: rs376178277; hg19: chr11-26708039; API