12-20721819-C-T

Variant summary

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

The NM_017435.5(SLCO1C1):​c.791C>T​(p.Thr264Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,978 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SLCO1C1
NM_017435.5 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.96
Variant links:
Genes affected
SLCO1C1 (HGNC:13819): (solute carrier organic anion transporter family member 1C1) This gene encodes a member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of thyroid hormones in brain tissues. This protein has particularly high affinity for the thyroid hormones thyroxine, tri-iodothyronine and reverse tri-iodothyronine. Polymorphisms in the gene encoding this protein may be associated with fatigue and depression in patients suffering from hyperthyroidism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

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
SLCO1C1NM_017435.5 linkc.791C>T p.Thr264Ile missense_variant Exon 8 of 15 ENST00000266509.7 NP_059131.1 Q9NYB5-1
SLCO1C1NM_001145946.2 linkc.791C>T p.Thr264Ile missense_variant Exon 9 of 16 NP_001139418.1 Q9NYB5-3
SLCO1C1NM_001145945.2 linkc.644C>T p.Thr215Ile missense_variant Exon 8 of 15 NP_001139417.1 Q9NYB5-2
SLCO1C1NM_001145944.2 linkc.437C>T p.Thr146Ile missense_variant Exon 6 of 13 NP_001139416.1 Q9NYB5-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLCO1C1ENST00000266509.7 linkc.791C>T p.Thr264Ile missense_variant Exon 8 of 15 1 NM_017435.5 ENSP00000266509.2 Q9NYB5-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152136
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251370
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135862
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461842
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152136
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 31, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.791C>T (p.T264I) alteration is located in exon 9 (coding exon 7) of the SLCO1C1 gene. This alteration results from a C to T substitution at nucleotide position 791, causing the threonine (T) at amino acid position 264 to be replaced by an isoleucine (I). 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
0.23
BayesDel_addAF
Uncertain
0.082
D
BayesDel_noAF
Uncertain
0.060
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.071
.;T;.;.
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Benign
0.025
T
MetaRNN
Uncertain
0.73
D;D;D;D
MetaSVM
Uncertain
-0.19
T
MutationAssessor
Pathogenic
3.8
.;H;H;.
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-5.1
D;D;D;D
REVEL
Uncertain
0.38
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.64
MutPred
0.67
.;Gain of catalytic residue at D259 (P = 2e-04);Gain of catalytic residue at D259 (P = 2e-04);.;
MVP
0.25
ClinPred
1.0
D
GERP RS
4.9
Varity_R
0.69
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs770797724; hg19: chr12-20874753; API