chr12-101157328-A-C

Variant names:

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

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.1784T>G​(p.Ile595Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 6.8e-7 (0 hom.)
• Consequence: SLC5A8 NM_145913.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: 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=0.0813621).

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>G	p.Ile595Ser	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>G	p.Ile595Ser	missense	Exon 15 of 15	ENSP00000445340.2	Q8N695
	SLC5A8	ENST00000957673.1		c.1718T>G	p.Ile573Ser	missense	Exon 14 of 14	ENSP00000627732.1
	SLC5A8	ENST00000957672.1		c.1598T>G	p.Ile533Ser	missense	Exon 12 of 12	ENSP00000627731.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461334 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726930

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111776

Other (OTH) AF: 0.00 AC: 0 AN: 60364

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	0.14
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.75	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.4
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.22
Sift	Benign	0.68	T
Sift4G	Benign	0.23	T
Polyphen		0.049	B
Vest4		0.31
MutPred		0.30		Loss of sheet (P = 0.003)
MVP		0.30
MPC		0.18
ClinPred		0.93	D
GERP RS		5.2
Varity_R		0.16
gMVP		0.58
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;