Variant chr12-20711408-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000266509.7(SLCO1C1):c.427C>A(p.Pro143Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,610,402 control chromosomes in the GnomAD database, including 1,860 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.034 ( 126 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1734 hom. )

Consequence

SLCO1C1
ENST00000266509.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0150

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017707348).

BP6

Variant 12-20711408-C-A is Benign according to our data. Variant chr12-20711408-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLCO1C1	NM_017435.5 linkuse as main transcript	c.427C>A	p.Pro143Thr	missense_variant	5/15	ENST00000266509.7	NP_059131.1
SLCO1C1	NM_001145946.2 linkuse as main transcript	c.427C>A	p.Pro143Thr	missense_variant	6/16		NP_001139418.1
SLCO1C1	NM_001145945.2 linkuse as main transcript	c.427C>A	p.Pro143Thr	missense_variant	6/15		NP_001139417.1
SLCO1C1	NM_001145944.2 linkuse as main transcript	c.73C>A	p.Pro25Thr	missense_variant	3/13		NP_001139416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1C1	ENST00000266509.7 linkuse as main transcript	c.427C>A	p.Pro143Thr	missense_variant	5/15	1	NM_017435.5	ENSP00000266509	P1	Q9NYB5-1

Frequencies

GnomAD3 genomes

AF:

0.0345

AC:

5250

AN:

152172

Hom.:

126

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00963

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.0517

Gnomad ASJ

AF:

0.0518

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0527

Gnomad OTH

AF:

0.0516

GnomAD3 exomes

AF:

0.0340

AC:

8523

AN:

250724

Hom.:

203

AF XY:

0.0348

AC XY:

4712

AN XY:

135482

show subpopulations

Gnomad AFR exome

AF:

0.0100

Gnomad AMR exome

AF:

0.0331

Gnomad ASJ exome

AF:

0.0522

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00786

Gnomad FIN exome

AF:

0.0148

Gnomad NFE exome

AF:

0.0520

Gnomad OTH exome

AF:

0.0387

GnomAD4 exome

AF:

0.0446

AC:

65096

AN:

1458112

Hom.:

1734

Cov.:

AF XY:

0.0443

AC XY:

32164

AN XY:

725480

show subpopulations

Gnomad4 AFR exome

AF:

0.00777

Gnomad4 AMR exome

AF:

0.0352

Gnomad4 ASJ exome

AF:

0.0546

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00827

Gnomad4 FIN exome

AF:

0.0155

Gnomad4 NFE exome

AF:

0.0521

Gnomad4 OTH exome

AF:

0.0396

GnomAD4 genome

AF:

0.0345

AC:

5247

AN:

152290

Hom.:

126

Cov.:

AF XY:

0.0322

AC XY:

2398

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00960

Gnomad4 AMR

AF:

0.0516

Gnomad4 ASJ

AF:

0.0518

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.0126

Gnomad4 NFE

AF:

0.0527

Gnomad4 OTH

AF:

0.0501

Alfa

AF:

0.0480

Hom.:

334

Bravo

AF:

0.0382

TwinsUK

AF:

0.0523

AC:

194

ALSPAC

AF:

0.0586

AC:

226

ESP6500AA

AF:

0.00953

AC:

ESP6500EA

AF:

0.0552

AC:

475

ExAC

AF:

0.0328

AC:

3983

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.0556

EpiControl

AF:

0.0610

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.6

DANN

Benign

0.86

DEOGEN2

Benign

0.0044

.;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.85

T;D;D;D

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

N;N;N;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.82

N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.53

T;T;T;T

Sift4G

Benign

0.78

T;T;T;T

Polyphen

0.022

.;B;.;.

Vest4

0.18

ClinPred

0.0012

GERP RS

-0.11

Varity_R

0.048

gMVP

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over