11-64556328-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018484.4(SLC22A11):​c.329C>T​(p.Thr110Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

SLC22A11
NM_018484.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16164565).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC22A11NM_018484.4 linkc.329C>T p.Thr110Met missense_variant Exon 1 of 10 ENST00000301891.9 NP_060954.1 Q9NSA0-1
SLC22A11NM_001307985.2 linkc.329C>T p.Thr110Met missense_variant Exon 1 of 8 NP_001294914.1 Q9NSA0-2
SLC22A11XM_011545167.2 linkc.34C>T p.Arg12Trp missense_variant Exon 1 of 9 XP_011543469.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC22A11ENST00000301891.9 linkc.329C>T p.Thr110Met missense_variant Exon 1 of 10 1 NM_018484.4 ENSP00000301891.4 Q9NSA0-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152224
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000519
AC:
13
AN:
250428
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135468
show subpopulations
Gnomad AFR exome
AF:
0.0000618
Gnomad AMR exome
AF:
0.000260
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000226
AC:
33
AN:
1461024
Hom.:
0
Cov.:
31
AF XY:
0.0000220
AC XY:
16
AN XY:
726882
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152224
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
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
Alfa
AF:
0.0000278
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

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

The c.329C>T (p.T110M) alteration is located in exon 1 (coding exon 1) of the SLC22A11 gene. This alteration results from a C to T substitution at nucleotide position 329, causing the threonine (T) at amino acid position 110 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
0.10
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T;.;T
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.051
N
LIST_S2
Uncertain
0.86
D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.7
M;M;.
PrimateAI
Benign
0.39
T
PROVEAN
Pathogenic
-5.0
D;D;D
REVEL
Benign
0.048
Sift
Benign
0.050
D;D;D
Sift4G
Uncertain
0.043
D;T;T
Polyphen
1.0
D;D;D
Vest4
0.15
MVP
0.33
MPC
0.78
ClinPred
0.82
D
GERP RS
-0.17
Varity_R
0.067
gMVP
0.64

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: rs140236068; hg19: chr11-64323800; API