11-26671139-C-A

Variant summary

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

The NM_178498.4(SLC5A12):​c.1820G>T​(p.Ser607Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,474 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: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC5A12
NM_178498.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.577
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=0.17554724).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC5A12NM_178498.4 linkc.1820G>T p.Ser607Ile missense_variant Exon 15 of 15 ENST00000396005.8 NP_848593.2 Q1EHB4-1
SLC5A12XM_006718155.4 linkc.1487G>T p.Ser496Ile missense_variant Exon 15 of 15 XP_006718218.1
SLC5A12XM_011519920.3 linkc.1256G>T p.Ser419Ile missense_variant Exon 16 of 16 XP_011518222.1
SLC5A12XM_017017244.2 linkc.1256G>T p.Ser419Ile missense_variant Exon 16 of 16 XP_016872733.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC5A12ENST00000396005.8 linkc.1820G>T p.Ser607Ile missense_variant Exon 15 of 15 1 NM_178498.4 ENSP00000379326.3 Q1EHB4-1
SLC5A12ENST00000527405.5 linkn.*426G>T non_coding_transcript_exon_variant Exon 15 of 15 2 ENSP00000436011.1 G3V1E3
SLC5A12ENST00000527405.5 linkn.*426G>T 3_prime_UTR_variant Exon 15 of 15 2 ENSP00000436011.1 G3V1E3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460474
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
726532
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 18, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1820G>T (p.S607I) alteration is located in exon 15 (coding exon 15) of the SLC5A12 gene. This alteration results from a G to T substitution at nucleotide position 1820, causing the serine (S) at amino acid position 607 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
Benign
0.12
BayesDel_addAF
Uncertain
0.063
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.011
T
Eigen
Benign
0.12
Eigen_PC
Benign
0.18
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.069
D
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-0.32
T
MutationAssessor
Benign
1.9
L
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.3
N
REVEL
Uncertain
0.44
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.010
D
Polyphen
0.72
P
Vest4
0.27
MutPred
0.33
Loss of disorder (P = 0.0152);
MVP
0.85
MPC
0.40
ClinPred
0.86
D
GERP RS
4.1
Varity_R
0.15
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-26692686; API