12-101170930-C-T

Variant names:

• chr12-101170930-C-T
• rs724344
• NM_145913.5:c.1234-2748G>A

Variant summary

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

The NM_145913.5(SLC5A8):​c.1234-2748G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,066 control chromosomes in the GnomAD database, including 4,253 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 0.23 (4253 hom., cov: 32)
• Consequence: SLC5A8 NM_145913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A8	NM_145913.5	c.1234-2748G>A		intron_variant	Intron 10 of 14	ENST00000536262.3	NP_666018.3
SLC5A8	XM_017018910.3	c.1234-2748G>A		intron_variant	Intron 10 of 11		XP_016874399.1
SLC5A8	XR_007063055.1	n.1624-2748G>A		intron_variant	Intron 10 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A8	ENST00000536262.3	c.1234-2748G>A		intron_variant	Intron 10 of 14	1	NM_145913.5	ENSP00000445340.2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34279 AN: 151948 Hom.: 4255 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.225 AC: 34284 AN: 152066 Hom.: 4253 Cov.: 32 AF XY: 0.232 AC XY: 17247 AN XY: 74320

African (AFR) AF: 0.198 AC: 8230 AN: 41492

American (AMR) AF: 0.176 AC: 2684 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 970 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2714 AN: 5144

South Asian (SAS) AF: 0.227 AC: 1092 AN: 4816

European-Finnish (FIN) AF: 0.313 AC: 3311 AN: 10562

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

European-Non Finnish (NFE) AF: 0.213 AC: 14509 AN: 67982

Other (OTH) AF: 0.226 AC: 478 AN: 2112

Alfa AF: 0.219 Hom.: 15082

Bravo AF: 0.218

Asia WGS AF: 0.317 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.79
PhyloP100		0.020
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: rs724344; hg19: chr12-101564708;