chr12-101194029-G-A

Variant names:

• chr12-101194029-G-A
• rs12305787
• NM_145913.5:c.538-250C>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.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
• Publications: 1 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=-0.88).
• 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 rank	MANE	Protein	UniProt
SLC5A8	NM_145913.5	c.538-250C>T		intron_variant	Intron 4 of 14	ENST00000536262.3	NP_666018.3
SLC5A8	XM_017018910.3	c.538-250C>T		intron_variant	Intron 4 of 11		XP_016874399.1
SLC5A8	XR_007063055.1	n.928-250C>T		intron_variant	Intron 4 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A8	ENST00000536262.3	c.538-250C>T		intron_variant	Intron 4 of 14	1	NM_145913.5	ENSP00000445340.2

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

African (AFR) AF: 0.270 AC: 11193 AN: 41470

American (AMR) AF: 0.207 AC: 3161 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3472

East Asian (EAS) AF: 0.130 AC: 672 AN: 5178

South Asian (SAS) AF: 0.161 AC: 774 AN: 4818

European-Finnish (FIN) AF: 0.162 AC: 1717 AN: 10586

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10705 AN: 67982

Other (OTH) AF: 0.188 AC: 396 AN: 2112

Alfa AF: 0.152 Hom.: 1109

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
PhyloP100		-0.28
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: rs12305787; hg19: chr12-101587807;