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rs35008345

chr11-64556141-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_018484.4(SLC22A11):c.142C>T(p.Arg48Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,614,162 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0042 ( 18 hom. )

Consequence

SLC22A11
NM_018484.4 stop_gained

Scores

2
3
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.92
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM4
?
    PM4 - Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants
Stoplost variant in NM_018484.4 Downstream stopcodon found after 569 codons.
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-64556141-C-T is Benign according to our data. Variant chr11-64556141-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038511.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC22A11NM_018484.4 linkuse as main transcriptc.142C>T p.Arg48Ter stop_gained 1/10 ENST00000301891.9
SLC22A11NM_001307985.2 linkuse as main transcriptc.142C>T p.Arg48Ter stop_gained 1/8
SLC22A11XM_011545167.2 linkuse as main transcriptc.-154C>T 5_prime_UTR_variant 1/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC22A11ENST00000301891.9 linkuse as main transcriptc.142C>T p.Arg48Ter stop_gained 1/101 NM_018484.4 P1Q9NSA0-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00267
AC:
407
AN:
152160
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000700
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.0173
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00122
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00415
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00288
AC:
725
AN:
251470
Hom.:
4
AF XY:
0.00283
AC XY:
385
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00123
Gnomad AMR exome
AF:
0.00159
Gnomad ASJ exome
AF:
0.0142
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00148
Gnomad NFE exome
AF:
0.00392
Gnomad OTH exome
AF:
0.00424
GnomAD4 exome
AF:
0.00425
AC:
6211
AN:
1461884
Hom.:
18
Cov.:
31
AF XY:
0.00408
AC XY:
2966
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00102
Gnomad4 AMR exome
AF:
0.00161
Gnomad4 ASJ exome
AF:
0.0132
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.00191
Gnomad4 NFE exome
AF:
0.00475
Gnomad4 OTH exome
AF:
0.00596
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00267
AC:
407
AN:
152278
Hom.:
4
Cov.:
32
AF XY:
0.00254
AC XY:
189
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.000698
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.0173
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00122
Gnomad4 NFE
AF:
0.00415
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00391
Hom.:
2
Bravo
AF:
0.00301
TwinsUK
AF:
0.00566
AC:
21
ALSPAC
AF:
0.00778
AC:
30
ESP6500AA
AF:
0.00114
AC:
5
ESP6500EA
AF:
0.00372
AC:
32
ExAC
?
    Exome Aggregation Consortium database
AF:
0.00260
AC:
316
Asia WGS
AF:
0.000289
AC:
2
AN:
3478
EpiCase
AF:
0.00382
EpiControl
AF:
0.00504

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

SLC22A11-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 08, 2022This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Pathogenic
0.57
Cadd
Pathogenic
36
Dann
Uncertain
1.0
Eigen
Uncertain
0.35
Eigen_PC
Benign
0.093
FATHMM_MKL
Uncertain
0.83
D
MutationTaster
Benign
1.0
A;A;A
Vest4
0.80
GERP RS
2.9

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: rs35008345; hg19: chr11-64323613; COSMIC: COSV99042481; API