12-101157328-A-G

Variant names:

• chr12-101157328-A-G
• rs1047902077
• NM_145913.5:c.1784T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145913.5(SLC5A8):​c.1784T>C​(p.Ile595Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I595S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC5A8 NM_145913.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060948968).

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.1784T>C	p.Ile595Thr	missense	Exon 15 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.1784T>C	p.Ile595Thr	missense	Exon 15 of 15	ENSP00000445340.2	Q8N695
	SLC5A8	ENST00000957673.1		c.1718T>C	p.Ile573Thr	missense	Exon 14 of 14	ENSP00000627732.1
	SLC5A8	ENST00000957672.1		c.1598T>C	p.Ile533Thr	missense	Exon 12 of 12	ENSP00000627731.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.54	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.4
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.21
Sift	Benign	0.59	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.093
MutPred		0.30		Loss of sheet (P = 0.0084)
MVP		0.27
MPC		0.13
ClinPred		0.22	T
GERP RS		5.2
Varity_R		0.13
gMVP		0.39
Mutation Taster		=82/18	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: rs1047902077; hg19: chr12-101551106;