Variant 12-101157287-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.24

Variant links:

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]

SLC5A8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A8	NM_145913.5 linkuse as main transcript	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 linkuse as main transcript	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.:

Cov.:

show subpopulations

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.:

AF XY:

0.00187

AC XY:

254

AN XY:

135472

show subpopulations

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.:

Cov.:

AF XY:

0.000886

AC XY:

644

AN XY:

726492

show subpopulations

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.:

Cov.:

AF XY:

0.00969

AC XY:

719

AN XY:

74230

show subpopulations

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.:

Bravo

AF:

0.0109

ESP6500AA

AF:

0.0329

AC:

145

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00314

AC:

381

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.95

MetaRNN

Benign

0.0048

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.98

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.45

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.016

Polyphen

0.98

Vest4

0.30

MVP

0.62

MPC

0.34

ClinPred

0.034

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over