rs779126291

Variant names:

• chr12-101157286-C-T
• rs779126291
• NM_145913.5:c.1826G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145913.5(SLC5A8):​c.1826G>A​(p.Arg609His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000571 in 1,612,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R609C) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: SLC5A8 NM_145913.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.106
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04210013).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145913.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A8	NM_145913.5	MANE Select	c.1826G>A	p.Arg609His	missense	Exon 15 of 15	NP_666018.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A8	ENST00000536262.3	TSL:1 MANE Select	c.1826G>A	p.Arg609His	missense	Exon 15 of 15	ENSP00000445340.2	Q8N695
	SLC5A8	ENST00000957673.1		c.1760G>A	p.Arg587His	missense	Exon 14 of 14	ENSP00000627732.1
	SLC5A8	ENST00000957672.1		c.1640G>A	p.Arg547His	missense	Exon 12 of 12	ENSP00000627731.1

Frequencies

GnomAD3 genomes AF: 0.0000593 AC: 9 AN: 151872 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000798 AC: 20 AN: 250654 AF XY: 0.0000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000490

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000568 AC: 83 AN: 1460486 Hom.: 0 Cov.: 31 AF XY: 0.0000468 AC XY: 34 AN XY: 726496

African (AFR) AF: 0.0000299 AC: 1 AN: 33434

American (AMR) AF: 0.0000449 AC: 2 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26084

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39654

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 86048

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111256

Other (OTH) AF: 0.0000332 AC: 2 AN: 60328

GnomAD4 genome AF: 0.0000593 AC: 9 AN: 151872 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74160

African (AFR) AF: 0.0000484 AC: 2 AN: 41360

American (AMR) AF: 0.00 AC: 0 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67978

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.000155 Hom.: 0

Bravo AF: 0.000106

ExAC AF: 0.0000824 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.5
DANN	Benign	0.92
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.18	N
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.11
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.21
Sift	Benign	0.27	T
Sift4G	Benign	0.46	T
Polyphen		0.0010	B
Vest4		0.11
MVP		0.21
MPC		0.13
ClinPred		0.043	T
GERP RS		1.6
Varity_R		0.026
gMVP		0.47
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs779126291; hg19: chr12-101551064;