chr11-64562023-C-A

Variant summary

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

The NM_018484.4(SLC22A11):​c.517C>A​(p.Leu173Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,248 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SLC22A11
NM_018484.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0490
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
SLC22A11NM_018484.4 linkc.517C>A p.Leu173Met missense_variant Exon 3 of 10 ENST00000301891.9 NP_060954.1 Q9NSA0-1
SLC22A11NM_001307985.2 linkc.517C>A p.Leu173Met missense_variant Exon 3 of 8 NP_001294914.1 Q9NSA0-2
SLC22A11XM_011545167.2 linkc.118C>A p.Leu40Met missense_variant Exon 2 of 9 XP_011543469.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC22A11ENST00000301891.9 linkc.517C>A p.Leu173Met missense_variant Exon 3 of 10 1 NM_018484.4 ENSP00000301891.4 Q9NSA0-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000800
AC:
2
AN:
250102
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135420
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461044
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726798
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.517C>A (p.L173M) alteration is located in exon 3 (coding exon 3) of the SLC22A11 gene. This alteration results from a C to A substitution at nucleotide position 517, causing the leucine (L) at amino acid position 173 to be replaced by a methionine (M). 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
Benign
0.24
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.23
T;.;T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.042
N
LIST_S2
Benign
0.70
T;T;T
M_CAP
Benign
0.040
D
MetaRNN
Uncertain
0.71
D;D;D
MetaSVM
Benign
-0.54
T
MutationAssessor
Uncertain
2.7
M;M;.
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.7
N;N;N
REVEL
Uncertain
0.31
Sift
Uncertain
0.0040
D;D;D
Sift4G
Uncertain
0.0070
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.55
MVP
0.76
MPC
0.75
ClinPred
0.24
T
GERP RS
-4.8
Varity_R
0.13
gMVP
0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370054919; hg19: chr11-64329495; API