NM_178498.4:c.1709A>G

Variant names:

• chr11-26671250-T-C
• rs1408140092
• NM_178498.4:c.1709A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178498.4(SLC5A12):​c.1709A>G​(p.Glu570Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000251 in 1,593,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC5A12 NM_178498.4 missense, splice_region
• Scores: Splicing: ADA: 0.1693
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12337494).

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.1709A>G	p.Glu570Gly	missense splice_region	Exon 15 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.1709A>G	p.Glu570Gly	missense splice_region	Exon 15 of 15	ENSP00000379326.3	Q1EHB4-1
	SLC5A12	ENST00000868799.1		c.1376A>G	p.Glu459Gly	missense splice_region	Exon 15 of 15	ENSP00000538858.1
	SLC5A12	ENST00000527405.5	TSL:2	n.*315A>G		splice_region non_coding_transcript_exon	Exon 15 of 15	ENSP00000436011.1	G3V1E3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152042 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000439 AC: 1 AN: 227944 AF XY: 0.00

Gnomad AFR exome AF: 0.0000677

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 6.94e-7 AC: 1 AN: 1441648 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 716568

African (AFR) AF: 0.0000308 AC: 1 AN: 32456

American (AMR) AF: 0.00 AC: 0 AN: 41780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25190

East Asian (EAS) AF: 0.00 AC: 0 AN: 38448

South Asian (SAS) AF: 0.00 AC: 0 AN: 83016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102750

Other (OTH) AF: 0.00 AC: 0 AN: 59428

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152042 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74270

African (AFR) AF: 0.0000724 AC: 3 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.074
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.28	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.8
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.21
Sift	Benign	0.14	T
Sift4G	Uncertain	0.014	D
Polyphen		0.089	B
Vest4		0.18
MutPred		0.20		Loss of helix (P = 0.0626)
MVP		0.88
MPC		0.25
ClinPred		0.21	T
GERP RS		5.0
Varity_R		0.10
gMVP		0.35
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.17
dbscSNV1_RF	Benign	0.50
SpliceAI score (max)		0.070		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: rs1408140092; hg19: chr11-26692797;