11-26671139-C-A

Variant names:

• chr11-26671139-C-A
• NM_178498.4:c.1820G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.577

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

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
SLC5A12	NM_178498.4	c.1820G>T	p.Ser607Ile	missense_variant	Exon 15 of 15	ENST00000396005.8	NP_848593.2
SLC5A12	XM_006718155.4	c.1487G>T	p.Ser496Ile	missense_variant	Exon 15 of 15		XP_006718218.1
SLC5A12	XM_011519920.3	c.1256G>T	p.Ser419Ile	missense_variant	Exon 16 of 16		XP_011518222.1
SLC5A12	XM_017017244.2	c.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
SLC5A12	ENST00000396005.8	c.1820G>T	p.Ser607Ile	missense_variant	Exon 15 of 15	1	NM_178498.4	ENSP00000379326.3
SLC5A12	ENST00000527405.5	n.*426G>T		non_coding_transcript_exon_variant	Exon 15 of 15	2		ENSP00000436011.1
SLC5A12	ENST00000527405.5	n.*426G>T		3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000436011.1

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

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

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;