11-26686492-C-T

Variant names:

• chr11-26686492-C-T
• rs376178277
• NM_178498.4:c.1206G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178498.4(SLC5A12):​c.1206G>A​(p.Met402Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC5A12 NM_178498.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178498.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A12	NM_178498.4	MANE Select	c.1206G>A	p.Met402Ile	missense	Exon 10 of 15	NP_848593.2	Q1EHB4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A12	ENST00000396005.8	TSL:1 MANE Select	c.1206G>A	p.Met402Ile	missense	Exon 10 of 15	ENSP00000379326.3	Q1EHB4-1
	SLC5A12	ENST00000868799.1		c.873G>A	p.Met291Ile	missense	Exon 10 of 15	ENSP00000538858.1
	SLC5A12	ENST00000527405.5	TSL:2	n.646G>A		non_coding_transcript_exon	Exon 10 of 15	ENSP00000436011.1	G3V1E3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	-0.044	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.6
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		0.62	D
GERP RS		2.6
Varity_R		0.37
gMVP		0.47
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs376178277; hg19: chr11-26708039; COSMIC: COSV105335702;