rs12785832

Positions:

• chr11-64559205-T-G

Variant summary

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

The NM_018484.4(SLC22A11):​c.464T>G​(p.Val155Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 31)
• Consequence: SLC22A11 NM_018484.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579

Genes affected

SLC22A11 (HGNC:18120): (solute carrier family 22 member 11) The protein encoded by this gene is 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 is found mainly in the kidney and in the placenta, where it may act to prevent potentially harmful organic anions from reaching the fetus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

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
SLC22A11	NM_018484.4	c.464T>G	p.Val155Gly	missense_variant	2/10	ENST00000301891.9	NP_060954.1
SLC22A11	NM_001307985.2	c.464T>G	p.Val155Gly	missense_variant	2/8		NP_001294914.1
SLC22A11	XM_011545167.2	c.99-2799T>G		intron_variant			XP_011543469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A11	ENST00000301891.9	c.464T>G	p.Val155Gly	missense_variant	2/10	1	NM_018484.4	ENSP00000301891	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000783 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D;.;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.48	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Uncertain	-0.030	T
MutationAssessor	Pathogenic	3.2	M;M;.
MutationTaster	Benign	0.77	N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-5.8	D;D;D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.96	D;P;D
Vest4		0.37
MutPred		0.28		Loss of stability (P = 0.0252);Loss of stability (P = 0.0252);Loss of stability (P = 0.0252);
MVP		0.70
MPC		0.35
ClinPred		0.75	D
GERP RS		2.2
Varity_R		0.48
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs12785832; hg19: chr11-64326677;