NM_178498.4:c.1619G>C

Variant names:

• chr11-26673490-C-G
• rs1201897929
• NM_178498.4:c.1619G>C

Variant summary

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

The NM_178498.4(SLC5A12):​c.1619G>C​(p.Arg540Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,456 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R540K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC5A12 NM_178498.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• 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.1619G>C	p.Arg540Thr	missense	Exon 14 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.1619G>C	p.Arg540Thr	missense	Exon 14 of 15	ENSP00000379326.3	Q1EHB4-1
	SLC5A12	ENST00000868799.1		c.1286G>C	p.Arg429Thr	missense	Exon 14 of 15	ENSP00000538858.1
	SLC5A12	ENST00000527405.5	TSL:2	n.*225G>C		non_coding_transcript_exon	Exon 14 of 15	ENSP00000436011.1	G3V1E3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459456 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725930

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33332

American (AMR) AF: 0.00 AC: 0 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39580

South Asian (SAS) AF: 0.00 AC: 0 AN: 85788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110846

Other (OTH) AF: 0.00 AC: 0 AN: 60302

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.095
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.8
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.69	N
REVEL	Uncertain	0.44
Sift	Benign	0.53	T
Sift4G	Benign	0.40	T
Polyphen		0.0040	B
Vest4		0.61
MutPred		0.52		Loss of MoRF binding (P = 0.0627)
MVP		0.81
MPC		0.47
ClinPred		0.59	D
GERP RS		5.6
Varity_R		0.16
gMVP		0.62
Mutation Taster		=51/49	polymorphism

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

Other links and lift over

dbSNP: rs1201897929; hg19: chr11-26695037;