12-20721879-T-C

Variant names:

• chr12-20721879-T-C
• NM_017435.5:c.851T>C

Variant summary

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

The NM_017435.5(SLCO1C1):​c.851T>C​(p.Ile284Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLCO1C1 NM_017435.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.46

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1C1	NM_017435.5	c.851T>C	p.Ile284Thr	missense_variant	Exon 8 of 15	ENST00000266509.7	NP_059131.1
SLCO1C1	NM_001145946.2	c.851T>C	p.Ile284Thr	missense_variant	Exon 9 of 16		NP_001139418.1
SLCO1C1	NM_001145945.2	c.704T>C	p.Ile235Thr	missense_variant	Exon 8 of 15		NP_001139417.1
SLCO1C1	NM_001145944.2	c.497T>C	p.Ile166Thr	missense_variant	Exon 6 of 13		NP_001139416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1C1	ENST00000266509.7	c.851T>C	p.Ile284Thr	missense_variant	Exon 8 of 15	1	NM_017435.5	ENSP00000266509.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727224

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	.;T;.;.
Eigen	Benign	-0.011
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.6	.;L;L;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.1	D;D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.015	D;D;D;D
Sift4G	Uncertain	0.0090	D;D;T;T
Polyphen		0.0030	.;B;.;.
Vest4		0.54
MutPred		0.60		.;Gain of catalytic residue at S285 (P = 8e-04);Gain of catalytic residue at S285 (P = 8e-04);.;
MVP		0.75
ClinPred		0.80	D
GERP RS		4.6
Varity_R		0.25
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-20874813;