Genetic Variant SLC5A12:p.Met391Thr (chr11-26686526-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_178498.4(SLC5A12):c.1172T>C(p.Met391Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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

SLC5A12
NM_178498.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.47

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]

SLC5A12 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33921474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A12	NM_178498.4 link	c.1172T>C	p.Met391Thr	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
SLC5A12	ENST00000396005.8 link	c.1172T>C	p.Met391Thr	missense_variant	Exon 10 of 15	1	NM_178498.4	ENSP00000379326.3		Q1EHB4-1
SLC5A12	ENST00000527405.5 link	n.612T>C		non_coding_transcript_exon_variant	Exon 10 of 15	2		ENSP00000436011.1		G3V1E3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461728

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727156

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1172T>C (p.M391T) alteration is located in exon 10 (coding exon 10) of the SLC5A12 gene. This alteration results from a T to C substitution at nucleotide position 1172, causing the methionine (M) at amino acid position 391 to be replaced by a threonine (T). 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

0.079

BayesDel_addAF

Benign

0.0037

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.017

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.80

M_CAP

Benign

0.068

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.62

MutationAssessor

Benign

-0.46

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.7

REVEL

Benign

0.28

Sift

Benign

0.067

Sift4G

Benign

0.067

Polyphen

0.0070

Vest4

0.53

MutPred

0.45

Gain of sheet (P = 0.0827);

MVP

0.56

MPC

0.25

ClinPred

0.22

GERP RS

5.5

Varity_R

0.20

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over