rs777534480

Variant names:

• chr12-101166587-T-G
• rs777534480
• NM_145913.5:c.1433A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145913.5(SLC5A8):​c.1433A>C​(p.Gln478Pro) 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 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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: 0.0000021 (0 hom.)
• Consequence: SLC5A8 NM_145913.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.336
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08310267).

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.1433A>C	p.Gln478Pro	missense	Exon 12 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.1433A>C	p.Gln478Pro	missense	Exon 12 of 15	ENSP00000445340.2	Q8N695
	SLC5A8	ENST00000957673.1		c.1367A>C	p.Gln456Pro	missense	Exon 11 of 14	ENSP00000627732.1
	SLC5A8	ENST00000957672.1		c.1247A>C	p.Gln416Pro	missense	Exon 9 of 12	ENSP00000627731.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251004 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461718 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727154

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111928

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

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	0.099
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	4.6
DANN	Benign	0.31
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.046	N
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.34
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.15
Sift	Benign	0.29	T
Sift4G	Benign	0.28	T
Polyphen		0.035	B
Vest4		0.19
MutPred		0.41		Loss of catalytic residue at Q478 (P = 0.0521)
MVP		0.17
MPC		0.13
ClinPred		0.047	T
GERP RS		2.8
Varity_R		0.20
gMVP		0.83
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs777534480; hg19: chr12-101560365;