12-101180039-G-A

Variant names:

• chr12-101180039-G-A
• NM_145913.5:c.1223C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2968402).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145913.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A8	NM_145913.5	MANE Select	c.1223C>T	p.Ala408Val	missense	Exon 10 of 15	NP_666018.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A8	ENST00000536262.3	TSL:1 MANE Select	c.1223C>T	p.Ala408Val	missense	Exon 10 of 15	ENSP00000445340.2	Q8N695
	SLC5A8	ENST00000957673.1		c.1157C>T	p.Ala386Val	missense	Exon 9 of 14	ENSP00000627732.1
	SLC5A8	ENST00000957672.1		c.1037C>T	p.Ala346Val	missense	Exon 7 of 12	ENSP00000627731.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461696 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727160

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111876

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	0.0056	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.74	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	-0.072	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.5
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.021	D
Polyphen		0.046	B
Vest4		0.35
MutPred		0.65		Gain of helix (P = 0.0199)
MVP		0.40
MPC		0.11
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.36
gMVP		0.59
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr12-101573817;