rs12785832

Variant names:

• chr11-64559205-T-A
• rs12785832
• NM_018484.4:c.464T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-64559205-T-A
• chr11-64559205-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018484.4(SLC22A11):​c.464T>A​(p.Val155Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,066 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC22A11 NM_018484.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A11	NM_018484.4	c.464T>A	p.Val155Glu	missense_variant	Exon 2 of 10	ENST00000301891.9	NP_060954.1
SLC22A11	NM_001307985.2	c.464T>A	p.Val155Glu	missense_variant	Exon 2 of 8		NP_001294914.1
SLC22A11	XM_011545167.2	c.99-2799T>A		intron_variant	Intron 1 of 8		XP_011543469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A11	ENST00000301891.9	c.464T>A	p.Val155Glu	missense_variant	Exon 2 of 10	1	NM_018484.4	ENSP00000301891.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459066 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725558

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.00 AC: 0 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39436

South Asian (SAS) AF: 0.00 AC: 0 AN: 86112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110218

Other (OTH) AF: 0.00 AC: 0 AN: 60228

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D;.;D
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.59	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Pathogenic	3.2	M;M;.
PhyloP100		0.58
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-5.0	D;D;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.98	D;D;D
Vest4		0.61
MutPred		0.60		Loss of MoRF binding (P = 0.0959);Loss of MoRF binding (P = 0.0959);Loss of MoRF binding (P = 0.0959);
MVP		0.72
MPC		0.93
ClinPred		0.87	D
GERP RS		2.2
Varity_R		0.49
gMVP		0.53
Mutation Taster		=94/6	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: rs12785832; hg19: chr11-64326677;