Variant 12-101180039-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145913.5(SLC5A8):c.1223C>T(p.Ala408Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC5A8
NM_145913.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2968402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC5A8	NM_145913.5 linkuse as main transcript	c.1223C>T	p.Ala408Val	missense_variant	10/15	ENST00000536262.3	NP_666018.3
SLC5A8	XM_017018910.3 linkuse as main transcript	c.1223C>T	p.Ala408Val	missense_variant	10/12		XP_016874399.1
SLC5A8	XR_007063055.1 linkuse as main transcript	n.1613C>T		non_coding_transcript_exon_variant	10/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A8	ENST00000536262.3 linkuse as main transcript	c.1223C>T	p.Ala408Val	missense_variant	10/15	1	NM_145913.5	ENSP00000445340	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000270

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

Jan 19, 2024

The c.1223C>T (p.A408V) alteration is located in exon 10 (coding exon 10) of the SLC5A8 gene. This alteration results from a C to T substitution at nucleotide position 1223, causing the alanine (A) at amino acid position 408 to be replaced by a valine (V). 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

0.19

BayesDel_addAF

Benign

0.0056

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.74

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.30

MetaSVM

Uncertain

-0.072

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.77

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.39

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.021

Polyphen

0.046

Vest4

0.35

MutPred

0.65

Gain of helix (P = 0.0199);

MVP

0.40

MPC

0.11

ClinPred

0.98

GERP RS

4.0

Varity_R

0.36

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over