11-62998967-G-C

Variant names:

• chr11-62998967-G-C
• rs11568496
• NM_004254.4:c.715C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004254.4(SLC22A8):​c.715C>G​(p.Gln239Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A8 NM_004254.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.05
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.86

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A8	NM_004254.4	c.715C>G	p.Gln239Glu	missense_variant	Exon 5 of 11	ENST00000336232.7	NP_004245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A8	ENST00000336232.7	c.715C>G	p.Gln239Glu	missense_variant	Exon 5 of 11	1	NM_004254.4	ENSP00000337335.2

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	Benign	0.23
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.74	D;.;.;T;D
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	.;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.86	D;D;D;D;D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Pathogenic	3.4	M;.;.;.;M
PhyloP100		5.0
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	N;N;N;N;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.018	D;D;T;D;D
Polyphen		1.0	D;.;.;.;D
Vest4		0.63
MutPred		0.73		Loss of stability (P = 0.1592);.;.;Loss of stability (P = 0.1592);Loss of stability (P = 0.1592);
MVP		0.57
MPC		1.1
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.72
gMVP		0.68
Mutation Taster		=85/15	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: rs11568496; hg19: chr11-62766439;