rs933087182

Variant names:

• chr11-62993509-C-T
• rs933087182
• NM_004254.4:c.1444G>A

Variant summary

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

The NM_004254.4(SLC22A8):​c.1444G>A​(p.Ala482Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.000032 (0 hom.)
• Consequence: SLC22A8 NM_004254.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51
• Publications: 1 publications found

Genes affected

SLC22A8 (HGNC:10972): (solute carrier family 22 member 8) This gene encodes a protein involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, May 2010]

ENSG00000301851 (HGNC:):

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=0.19812873).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004254.4. 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
	SLC22A8	NM_004254.4	MANE Select	c.1444G>A	p.Ala482Thr	missense	Exon 10 of 11	NP_004245.2
	SLC22A8	NM_001184732.2		c.1444G>A	p.Ala482Thr	missense	Exon 10 of 11	NP_001171661.1	Q8TCC7-1
	SLC22A8	NM_001184733.2		c.1171G>A	p.Ala391Thr	missense	Exon 10 of 11	NP_001171662.1	Q8TCC7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A8	ENST00000336232.7	TSL:1 MANE Select	c.1444G>A	p.Ala482Thr	missense	Exon 10 of 11	ENSP00000337335.2	Q8TCC7-1
	SLC22A8	ENST00000430500.6	TSL:1	c.1444G>A	p.Ala482Thr	missense	Exon 10 of 11	ENSP00000398548.2	Q8TCC7-1
	SLC22A8	ENST00000311438.12	TSL:1	c.1444G>A	p.Ala482Thr	missense	Exon 9 of 9	ENSP00000311463.8	H7BXN9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251378 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: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000322 AC: 47 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22 AN XY: 727248

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1112010

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

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	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.5
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.13
Sift	Benign	0.10	T
Sift4G	Benign	0.19	T
Polyphen		0.21	B
Vest4		0.041
MutPred		0.55		Loss of stability (P = 0.0729)
MVP		0.25
MPC		0.35
ClinPred		0.092	T
GERP RS		-1.0
Varity_R		0.066
gMVP		0.40
Mutation Taster		=99/1	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: rs933087182; hg19: chr11-62760981; COSMIC: COSV100267901; COSMIC: COSV100267901;