chr12-101208569-G-A

Variant names:

• chr12-101208569-G-A
• rs7962305
• NM_145913.5:c.351+929C>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.351+929C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 150,348 control chromosomes in the GnomAD database, including 5,370 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 0.26 (5370 hom., cov: 31)
• Consequence: SLC5A8 NM_145913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 4 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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A8	NM_145913.5	c.351+929C>T		intron_variant	Intron 1 of 14	ENST00000536262.3	NP_666018.3
SLC5A8	XM_017018910.3	c.351+929C>T		intron_variant	Intron 1 of 11		XP_016874399.1
SLC5A8	XR_007063055.1	n.741+929C>T		intron_variant	Intron 1 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A8	ENST00000536262.3	c.351+929C>T		intron_variant	Intron 1 of 14	1	NM_145913.5	ENSP00000445340.2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 38710 AN: 150230 Hom.: 5373 Cov.: 31

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.257 AC: 38712 AN: 150348 Hom.: 5370 Cov.: 31 AF XY: 0.261 AC XY: 19162 AN XY: 73364

African (AFR) AF: 0.246 AC: 10065 AN: 40930

American (AMR) AF: 0.176 AC: 2653 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 863 AN: 3456

East Asian (EAS) AF: 0.563 AC: 2861 AN: 5082

South Asian (SAS) AF: 0.158 AC: 734 AN: 4644

European-Finnish (FIN) AF: 0.379 AC: 3891 AN: 10260

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16817 AN: 67580

Other (OTH) AF: 0.248 AC: 519 AN: 2096

Alfa AF: 0.245 Hom.: 19347

Bravo AF: 0.245

Asia WGS AF: 0.318 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.68
PhyloP100		-0.21
Mutation Taster		=100/0	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: rs7962305; hg19: chr12-101602347;