Variant chr12-101182846-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145913.5(SLC5A8):c.1122A>T(p.Arg374Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,443,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC5A8
NM_145913.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.261

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1296454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A8	NM_145913.5 link	c.1122A>T	p.Arg374Ser	missense_variant	9/15	ENST00000536262.3	NP_666018.3	Q8N695
SLC5A8	XM_017018910.3 link	c.1122A>T	p.Arg374Ser	missense_variant	9/12		XP_016874399.1
SLC5A8	XR_007063055.1 link	n.1512A>T		non_coding_transcript_exon_variant	9/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A8	ENST00000536262.3 link	c.1122A>T	p.Arg374Ser	missense_variant	9/15	1	NM_145913.5	ENSP00000445340.2		Q8N695

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000857

AC:

AN:

233478

Hom.:

AF XY:

0.00000790

AC XY:

AN XY:

126550

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000672

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1443980

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000488

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

The c.1122A>T (p.R374S) alteration is located in exon 9 (coding exon 9) of the SLC5A8 gene. This alteration results from a A to T substitution at nucleotide position 1122, causing the arginine (R) at amino acid position 374 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.33

CADD

Benign

7.7

DANN

Benign

0.90

DEOGEN2

Benign

0.11

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.096

M_CAP

Benign

0.083

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.17

REVEL

Benign

0.20

Sift

Benign

0.10

Sift4G

Benign

0.21

Polyphen

0.040

Vest4

0.23

MutPred

0.58

Gain of disorder (P = 0.0665);

MVP

0.13

MPC

0.12

ClinPred

0.087

GERP RS

-4.5

Varity_R

0.13

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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