12-20721938-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017435.5(SLCO1C1):c.910A>G(p.Ser304Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLCO1C1 NM_017435.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.355

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]

ACMG classification

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=0.099946946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1C1	NM_017435.5	c.910A>G	p.Ser304Gly	missense_variant	8/15	ENST00000266509.7
SLCO1C1	NM_001145946.2	c.910A>G	p.Ser304Gly	missense_variant	9/16
SLCO1C1	NM_001145945.2	c.763A>G	p.Ser255Gly	missense_variant	8/15
SLCO1C1	NM_001145944.2	c.556A>G	p.Ser186Gly	missense_variant	6/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1C1	ENST00000266509.7	c.910A>G	p.Ser304Gly	missense_variant	8/15	1	NM_017435.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2022

The c.910A>G (p.S304G) alteration is located in exon 9 (coding exon 7) of the SLCO1C1 gene. This alteration results from a A to G substitution at nucleotide position 910, causing the serine (S) at amino acid position 304 to be replaced by a glycine (G). 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	0.062
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	9.1
Dann	Benign	0.55
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.43	T;T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.060	N;N;N;N
REVEL	Benign	0.031
Sift	Benign	0.46	T;T;T;T
Sift4G	Benign	0.48	T;T;T;T
Polyphen		0.0	.;B;.;.
Vest4		0.098
MutPred		0.37		.;Loss of phosphorylation at S304 (P = 0.0038);Loss of phosphorylation at S304 (P = 0.0038);.;
MVP		0.030
ClinPred		0.072	T
GERP RS		3.5
Varity_R		0.067
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-20874872;