chr12-101193740-C-T

Position:

• chr12-101193740-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145913.5(SLC5A8):​c.577G>A​(p.Val193Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,613,642 control chromosomes in the GnomAD database, including 42,781 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.22 (4183 hom., cov: 32)
  • Exomes 𝑓: 0.22 (38598 hom.)
• Consequence: SLC5A8 NM_145913.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

Genes affected

SLC5A8 (HGNC:19119): (solute carrier family 5 member 8) SLC5A8 has been shown to transport iodide by a passive mechanism (Rodriguez et al., 2002 [PubMed 12107270]) and monocarboxylates and short-chain fatty acids by a sodium-coupled mechanism (Gopal et al., 2004 [PubMed 15322102]). In kidney, SLC5A8 functions as a high-affinity sodium-coupled lactate transporter involved in reabsorption of lactate and maintenance of blood lactate levels (Thangaraju et al., 2006 [PubMed 16873376]).[supplied by OMIM, Dec 2008]

SLC5A8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.3216925E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A8	NM_145913.5	c.577G>A	p.Val193Ile	missense_variant	5/15	ENST00000536262.3	NP_666018.3
SLC5A8	XM_017018910.3	c.577G>A	p.Val193Ile	missense_variant	5/12		XP_016874399.1
SLC5A8	XR_007063055.1	n.967G>A		non_coding_transcript_exon_variant	5/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A8	ENST00000536262.3	c.577G>A	p.Val193Ile	missense_variant	5/15	1	NM_145913.5	ENSP00000445340.2

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33947 AN: 151942 Hom.: 4181 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.226

GnomAD3 exomes AF: 0.238 AC: 59803 AN: 251342 Hom.: 8466 AF XY: 0.239 AC XY: 32440 AN XY: 135834

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.127

Gnomad ASJ exome AF: 0.273

Gnomad EAS exome AF: 0.550

Gnomad SAS exome AF: 0.214

Gnomad FIN exome AF: 0.313

Gnomad NFE exome AF: 0.216

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.222 AC: 324120 AN: 1461582 Hom.: 38598 Cov.: 33 AF XY: 0.223 AC XY: 161906 AN XY: 727088

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.277

Gnomad4 EAS exome AF: 0.522

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.223 AC: 33963 AN: 152060 Hom.: 4183 Cov.: 32 AF XY: 0.230 AC XY: 17122 AN XY: 74334

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.226

Alfa AF: 0.224 Hom.: 8821

Bravo AF: 0.215

TwinsUK AF: 0.197 AC: 731

ALSPAC AF: 0.205 AC: 790

ESP6500AA AF: 0.186 AC: 819

ESP6500EA AF: 0.224 AC: 1930

ExAC AF: 0.239 AC: 29047

Asia WGS AF: 0.317 AC: 1101 AN: 3478

EpiCase AF: 0.227

EpiControl AF: 0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.062
FATHMM_MKL	Benign	0.73	D
MetaRNN	Benign	0.000053	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.33	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.19
Sift	Benign	0.24	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.19
MPC		0.086
ClinPred		0.014	T
GERP RS		3.6
Varity_R		0.073
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs1709189; hg19: chr12-101587518; COSMIC: COSV73310349;