Variant 12-20737157-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017435.5(SLCO1C1):c.1433C>T(p.Ser478Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000449 in 1,559,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S478T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

SLCO1C1
NM_017435.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

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]

SLCO1C1 links:

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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/exons	MANE
SLCO1C1	NM_017435.5 linkuse as main transcript	c.1433C>T	p.Ser478Leu	missense_variant	11/15	ENST00000266509.7
SLCO1C1	NM_001145946.2 linkuse as main transcript	c.1433C>T	p.Ser478Leu	missense_variant	12/16
SLCO1C1	NM_001145945.2 linkuse as main transcript	c.1286C>T	p.Ser429Leu	missense_variant	11/15
SLCO1C1	NM_001145944.2 linkuse as main transcript	c.1079C>T	p.Ser360Leu	missense_variant	9/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1C1	ENST00000266509.7 linkuse as main transcript	c.1433C>T	p.Ser478Leu	missense_variant	11/15	1	NM_017435.5	P1	Q9NYB5-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152112

Hom.:

Cov.:

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000986

AC:

AN:

202868

Hom.:

AF XY:

0.0000180

AC XY:

AN XY:

110868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000894

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000426

AC:

AN:

1407098

Hom.:

Cov.:

AF XY:

0.00000716

AC XY:

AN XY:

698622

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:

0.0000786

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74296

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.1433C>T (p.S478L) alteration is located in exon 12 (coding exon 10) of the SLCO1C1 gene. This alteration results from a C to T substitution at nucleotide position 1433, causing the serine (S) at amino acid position 478 to be replaced by a leucine (L). 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

0.081

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.37

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

0.027

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.0084

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-0.73

MutationTaster

Benign

0.80

D;D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.6

D;D;D;D

REVEL

Benign

0.078

Sift

Benign

0.062

T;D;D;D

Sift4G

Benign

0.11

T;T;D;D

Polyphen

0.0060

.;B;.;.

Vest4

0.34

MutPred

0.48

.;Gain of catalytic residue at N477 (P = 0);Gain of catalytic residue at N477 (P = 0);.;

MVP

0.14

ClinPred

0.92

GERP RS

5.0

Varity_R

0.30

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.23

Position offset: -50

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over