rs12305787

chr12-101194029-G-Achr12-101194029-G-C

Variant summary

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

The NM_145913.5(SLC5A8):c.538-250C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,114 control chromosomes in the GnomAD database, including 3,192 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 (3192 hom., cov: 32)
• Consequence: SLC5A8 NM_145913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A8	NM_145913.5	c.538-250C>T		intron_variant		ENST00000536262.3
SLC5A8	XM_017018910.3	c.538-250C>T		intron_variant
SLC5A8	XR_007063055.1	n.928-250C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A8	ENST00000536262.3	c.538-250C>T		intron_variant		1	NM_145913.5	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29301 AN: 151996 Hom.: 3191 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29314 AN: 152114 Hom.: 3192 Cov.: 32 AF XY: 0.192 AC XY: 14281 AN XY: 74346

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.188

Alfa AF: 0.151 Hom.: 1015

Bravo AF: 0.200

Asia WGS AF: 0.177 AC: 615 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.23
Dann	Benign	0.67

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: rs12305787; hg19: chr12-101587807;