12-101157325-T-C

Variant names:

• chr12-101157325-T-C
• NM_145913.5:c.1787A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145913.5(SLC5A8):​c.1787A>G​(p.Glu596Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC5A8 NM_145913.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.36

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 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=0.29791635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A8	NM_145913.5	c.1787A>G	p.Glu596Gly	missense_variant	Exon 15 of 15	ENST00000536262.3	NP_666018.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A8	ENST00000536262.3	c.1787A>G	p.Glu596Gly	missense_variant	Exon 15 of 15	1	NM_145913.5	ENSP00000445340.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461362 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726948

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.50
Sift	Benign	0.055	T
Sift4G	Benign	0.10	T
Polyphen		0.034	B
Vest4		0.53
MutPred		0.32		Loss of catalytic residue at E596 (P = 0.0045);
MVP		0.44
MPC		0.53
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.15
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-101551103;