12-101157287-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_145913.5(SLC5A8):c.1825C>T(p.Arg609Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00188 in 1,612,462 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R609H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.010 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (17 hom.)
• Consequence: SLC5A8 NM_145913.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.24

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048193336).
• BP6: Variant 12-101157287-G-A is Benign according to our data. Variant chr12-101157287-G-A is described in ClinVar as [Benign]. Clinvar id is 768573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1522/151950) while in subpopulation AFR AF= 0.0347 (1439/41458). AF 95% confidence interval is 0.0332. There are 22 homozygotes in gnomad4. There are 719 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A8	NM_145913.5	c.1825C>T	p.Arg609Cys	missense_variant	15/15	ENST00000536262.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A8	ENST00000536262.3	c.1825C>T	p.Arg609Cys	missense_variant	15/15	1	NM_145913.5	P1

Frequencies

GnomAD3 genomes AF: 0.00998 AC: 1515 AN: 151832 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00388

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00768

GnomAD3 exomes AF: 0.00257 AC: 645 AN: 250664 Hom.: 7 AF XY: 0.00187 AC XY: 254 AN XY: 135472

Gnomad AFR exome AF: 0.0340

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000882

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00103 AC: 1507 AN: 1460512 Hom.: 17 Cov.: 31 AF XY: 0.000886 AC XY: 644 AN XY: 726492

Gnomad4 AFR exome AF: 0.0342

Gnomad4 AMR exome AF: 0.00254

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000873

Gnomad4 OTH exome AF: 0.00230

GnomAD4 genome AF: 0.0100 AC: 1522 AN: 151950 Hom.: 22 Cov.: 32 AF XY: 0.00969 AC XY: 719 AN XY: 74230

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.00387

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00760

Alfa AF: 0.00171 Hom.: 4

Bravo AF: 0.0109

ESP6500AA AF: 0.0329 AC: 145

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00314 AC: 381

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.13
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.95	D
MetaRNN	Benign	0.0048	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	0.98	D
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.45
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.016	D
Polyphen		0.98	D
Vest4		0.30
MVP		0.62
MPC		0.34
ClinPred		0.034	T
GERP RS		5.2
Varity_R		0.15
gMVP		0.55

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: rs113062899; hg19: chr12-101551065;