rs2279834

Positions:

• chr12-101156398-T-C

Variant summary

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

The NM_145913.5(SLC5A8):​c.*881A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,742 control chromosomes in the GnomAD database, including 2,987 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (2987 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SLC5A8 NM_145913.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A8	NM_145913.5	c.*881A>G		3_prime_UTR_variant	15/15	ENST00000536262.3	NP_666018.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A8	ENST00000536262.3	c.*881A>G		3_prime_UTR_variant	15/15	1	NM_145913.5	ENSP00000445340.2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28204 AN: 151622 Hom.: 2983 Cov.: 32

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.186 AC: 28201 AN: 151740 Hom.: 2987 Cov.: 32 AF XY: 0.184 AC XY: 13656 AN XY: 74154

Gnomad4 AFR AF: 0.0863

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.200

Alfa AF: 0.226 Hom.: 2248

Bravo AF: 0.183

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.8
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs2279834; hg19: chr12-101550176;