11-64556350-G-C

Position:

• chr11-64556350-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018484.4(SLC22A11):​c.351G>C​(p.Trp117Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A11 NM_018484.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.79

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.931

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A11	NM_018484.4	c.351G>C	p.Trp117Cys	missense_variant	1/10	ENST00000301891.9	NP_060954.1
SLC22A11	NM_001307985.2	c.351G>C	p.Trp117Cys	missense_variant	1/8		NP_001294914.1
SLC22A11	XM_011545167.2	c.56G>C	p.Gly19Ala	missense_variant	1/9		XP_011543469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A11	ENST00000301891.9	c.351G>C	p.Trp117Cys	missense_variant	1/10	1	NM_018484.4	ENSP00000301891.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2024

The c.351G>C (p.W117C) alteration is located in exon 1 (coding exon 1) of the SLC22A11 gene. This alteration results from a G to C substitution at nucleotide position 351, causing the tryptophan (W) at amino acid position 117 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D;.;T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D;D;D
M_CAP	Uncertain	0.29	D
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Pathogenic	3.9	H;H;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-12	D;D;D
REVEL	Pathogenic	0.80
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.82
MutPred		0.69		Loss of catalytic residue at W117 (P = 0.0511);Loss of catalytic residue at W117 (P = 0.0511);Loss of catalytic residue at W117 (P = 0.0511);
MVP		0.88
MPC		0.97
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.88
gMVP		0.95

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-64323822;