Genetic Variant NM_017435.5:c.370C>G (chr12-20706047-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017435.5(SLCO1C1):c.370C>G(p.Leu124Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLCO1C1
NM_017435.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.565

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06915873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1C1	NM_017435.5 link	c.370C>G	p.Leu124Val	missense_variant	Exon 4 of 15	ENST00000266509.7	NP_059131.1	Q9NYB5-1
SLCO1C1	NM_001145946.2 link	c.370C>G	p.Leu124Val	missense_variant	Exon 5 of 16		NP_001139418.1	Q9NYB5-3
SLCO1C1	NM_001145945.2 link	c.370C>G	p.Leu124Val	missense_variant	Exon 5 of 15		NP_001139417.1	Q9NYB5-2
SLCO1C1	NM_001145944.2 link	c.16C>G	p.Leu6Val	missense_variant	Exon 2 of 13		NP_001139416.1	Q9NYB5-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1C1	ENST00000266509.7 link	c.370C>G	p.Leu124Val	missense_variant	Exon 4 of 15	1	NM_017435.5	ENSP00000266509.2		Q9NYB5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250810

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460922

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726744

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.370C>G (p.L124V) alteration is located in exon 5 (coding exon 3) of the SLCO1C1 gene. This alteration results from a C to G substitution at nucleotide position 370, causing the leucine (L) at amino acid position 124 to be replaced by a valine (V). 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

-0.40

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.014

DANN

Benign

0.77

DEOGEN2

Benign

0.0029

.;T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.53

T;T;T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.069

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L;L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.53

N;N;N;N

REVEL

Benign

0.078

Sift

Benign

0.49

T;T;T;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.0010

.;B;.;.

Vest4

0.33

MutPred

0.58

Gain of catalytic residue at G120 (P = 0);Gain of catalytic residue at G120 (P = 0);Gain of catalytic residue at G120 (P = 0);.;

MVP

0.12

ClinPred

0.032

GERP RS

-10

Varity_R

0.034

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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