rs11568493

Positions:

• chr11-62996135-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004254.4(SLC22A8):​c.779T>G​(p.Ile260Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A8 NM_004254.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.73

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A8	NM_004254.4	c.779T>G	p.Ile260Arg	missense_variant	6/11	ENST00000336232.7	NP_004245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A8	ENST00000336232.7	c.779T>G	p.Ile260Arg	missense_variant	6/11	1	NM_004254.4	ENSP00000337335	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;.;.;T;T
Eigen	Benign	-0.012
Eigen_PC	Benign	-0.033
FATHMM_MKL	Benign	0.24	N
LIST_S2	Uncertain	0.93	.;D;D;D;T
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.50	T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.1	M;.;.;.;M
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.5	N;N;N;N;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0060	D;D;D;D;D
Sift4G	Uncertain	0.019	D;D;T;D;D
Polyphen		0.47	P;.;.;.;P
Vest4		0.57
MutPred		0.23		Gain of disorder (P = 0.0342);.;.;Gain of disorder (P = 0.0342);Gain of disorder (P = 0.0342);
MVP		0.55
MPC		1.4
ClinPred		0.90	D
GERP RS		4.9
Varity_R		0.71
gMVP		0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs11568493; hg19: chr11-62763607;