chr12-101182846-T-A

Variant names:

• chr12-101182846-T-A
• rs1221128835
• NM_145913.5:c.1122A>T

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.1122A>T​(p.Arg374Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,443,980 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: 0.0000014 (0 hom.)
• Consequence: SLC5A8 NM_145913.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.261
• 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=0.1296454).

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.1122A>T	p.Arg374Ser	missense	Exon 9 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.1122A>T	p.Arg374Ser	missense	Exon 9 of 15	ENSP00000445340.2	Q8N695
	SLC5A8	ENST00000957673.1		c.1056A>T	p.Arg352Ser	missense	Exon 8 of 14	ENSP00000627732.1
	SLC5A8	ENST00000957672.1		c.936A>T	p.Arg312Ser	missense	Exon 6 of 12	ENSP00000627731.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000857 AC: 2 AN: 233478 AF XY: 0.00000790

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000672

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1443980 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 718014

African (AFR) AF: 0.00 AC: 0 AN: 32158

American (AMR) AF: 0.0000488 AC: 2 AN: 41008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25852

East Asian (EAS) AF: 0.00 AC: 0 AN: 38182

South Asian (SAS) AF: 0.00 AC: 0 AN: 82440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105612

Other (OTH) AF: 0.00 AC: 0 AN: 59706

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	7.7
DANN	Benign	0.90
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.096	N
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.26
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.20
Sift	Benign	0.10	T
Sift4G	Benign	0.21	T
Polyphen		0.040	B
Vest4		0.23
MutPred		0.58		Gain of disorder (P = 0.0665)
MVP		0.13
MPC		0.12
ClinPred		0.087	T
GERP RS		-4.5
Varity_R		0.13
gMVP		0.33
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1221128835; hg19: chr12-101576624;