rs164365

Variant names:

• chr12-101166550-C-A
• rs164365
• NM_145913.5:c.1470G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-101166550-C-A
• chr12-101166550-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145913.5(SLC5A8):​c.1470G>T​(p.Met490Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,612,632 control chromosomes in the GnomAD database, including 42,207 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. M490L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.21 (3819 hom., cov: 32)
  • Exomes 𝑓: 0.22 (38388 hom.)
• Consequence: SLC5A8 NM_145913.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241
• Publications: 21 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.911971E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145913.5. 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
	SLC5A8	NM_145913.5	MANE Select	c.1470G>T	p.Met490Ile	missense	Exon 12 of 15	NP_666018.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A8	ENST00000536262.3	TSL:1 MANE Select	c.1470G>T	p.Met490Ile	missense	Exon 12 of 15	ENSP00000445340.2	Q8N695
	SLC5A8	ENST00000957673.1		c.1404G>T	p.Met468Ile	missense	Exon 11 of 14	ENSP00000627732.1
	SLC5A8	ENST00000957672.1		c.1284G>T	p.Met428Ile	missense	Exon 9 of 12	ENSP00000627731.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31659 AN: 151896 Hom.: 3823 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.218

GnomAD2 exomes AF: 0.234 AC: 58529 AN: 250660 AF XY: 0.235

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.551

Gnomad FIN exome AF: 0.312

Gnomad NFE exome AF: 0.216

Gnomad OTH exome AF: 0.230

GnomAD4 exome AF: 0.220 AC: 322031 AN: 1460618 Hom.: 38388 Cov.: 33 AF XY: 0.222 AC XY: 160998 AN XY: 726614

African (AFR) AF: 0.135 AC: 4520 AN: 33458

American (AMR) AF: 0.128 AC: 5705 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 7172 AN: 26100

East Asian (EAS) AF: 0.524 AC: 20784 AN: 39674

South Asian (SAS) AF: 0.220 AC: 18989 AN: 86134

European-Finnish (FIN) AF: 0.303 AC: 16160 AN: 53376

Middle Eastern (MID) AF: 0.275 AC: 1581 AN: 5758

European-Non Finnish (NFE) AF: 0.210 AC: 233058 AN: 1111144

Other (OTH) AF: 0.233 AC: 14062 AN: 60342

GnomAD4 genome AF: 0.208 AC: 31648 AN: 152014 Hom.: 3819 Cov.: 32 AF XY: 0.216 AC XY: 16029 AN XY: 74304

African (AFR) AF: 0.138 AC: 5717 AN: 41478

American (AMR) AF: 0.169 AC: 2590 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3468

East Asian (EAS) AF: 0.528 AC: 2721 AN: 5156

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4818

European-Finnish (FIN) AF: 0.314 AC: 3314 AN: 10546

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14490 AN: 67950

Other (OTH) AF: 0.218 AC: 461 AN: 2116

Alfa AF: 0.218 Hom.: 15242

Bravo AF: 0.198

TwinsUK AF: 0.198 AC: 733

ALSPAC AF: 0.206 AC: 793

ESP6500AA AF: 0.135 AC: 597

ESP6500EA AF: 0.225 AC: 1932

ExAC AF: 0.234 AC: 28443

Asia WGS AF: 0.312 AC: 1084 AN: 3478

EpiCase AF: 0.227

EpiControl AF: 0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.1
DANN	Benign	0.44
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.026	N
MetaRNN	Benign	0.000089	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.24
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.099
Sift	Benign	0.43	T
Sift4G	Benign	0.43	T
Polyphen		0.0020	B
Vest4		0.039
MutPred		0.39		Loss of sheet (P = 0.0315)
MPC		0.12
ClinPred		0.0069	T
GERP RS		3.0
Varity_R		0.11
gMVP		0.54
Mutation Taster		=97/3	polymorphism (auto)

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: rs164365; hg19: chr12-101560328; COSMIC: COSV73310348;