Variant 12-20723234-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_017435.5(SLCO1C1):c.1166C>T(p.Ser389Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00719 in 1,613,790 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 16 hom., cov: 33)

Exomes 𝑓: 0.0072 ( 77 hom. )

Consequence

SLCO1C1
NM_017435.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.32

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008827329).

BP6

Variant 12-20723234-C-T is Benign according to our data. Variant chr12-20723234-C-T is described in ClinVar as [Benign]. Clinvar id is 790367.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-20723234-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLCO1C1	NM_017435.5 linkuse as main transcript	c.1166C>T	p.Ser389Phe	missense_variant	9/15	ENST00000266509.7
SLCO1C1	NM_001145946.2 linkuse as main transcript	c.1166C>T	p.Ser389Phe	missense_variant	10/16
SLCO1C1	NM_001145945.2 linkuse as main transcript	c.1019C>T	p.Ser340Phe	missense_variant	9/15
SLCO1C1	NM_001145944.2 linkuse as main transcript	c.812C>T	p.Ser271Phe	missense_variant	7/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1C1	ENST00000266509.7 linkuse as main transcript	c.1166C>T	p.Ser389Phe	missense_variant	9/15	1	NM_017435.5	P1	Q9NYB5-1

Frequencies

GnomAD3 genomes

AF:

0.00699

AC:

1063

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0399

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00663

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00749

AC:

1881

AN:

250988

Hom.:

AF XY:

0.00765

AC XY:

1038

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00381

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00341

Gnomad FIN exome

AF:

0.0395

Gnomad NFE exome

AF:

0.00629

Gnomad OTH exome

AF:

0.00703

GnomAD4 exome

AF:

0.00721

AC:

10534

AN:

1461516

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

5241

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.000867

Gnomad4 AMR exome

AF:

0.00425

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00309

Gnomad4 FIN exome

AF:

0.0352

Gnomad4 NFE exome

AF:

0.00696

Gnomad4 OTH exome

AF:

0.00679

GnomAD4 genome

AF:

0.00698

AC:

1063

AN:

152274

Hom.:

Cov.:

AF XY:

0.00831

AC XY:

619

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00614

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0399

Gnomad4 NFE

AF:

0.00663

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00573

Hom.:

Bravo

AF:

0.00439

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00667

AC:

810

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00583

EpiControl

AF:

0.00457

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.0

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;D;D

MetaRNN

Benign

0.0088

T;T;T;T

MetaSVM

Uncertain

-0.13

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-5.5

D;D;D;D

REVEL

Uncertain

0.59

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

.;D;.;.

Vest4

0.77

MVP

0.56

ClinPred

0.033

GERP RS

4.5

Varity_R

0.89

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over