12-20711408-C-T

Variant names:

• chr12-20711408-C-T
• rs36010656
• NM_017435.5:c.427C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017435.5(SLCO1C1):​c.427C>T​(p.Pro143Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P143T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SLCO1C1 NM_017435.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028769612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1C1	NM_017435.5	c.427C>T	p.Pro143Ser	missense_variant	Exon 5 of 15	ENST00000266509.7	NP_059131.1
SLCO1C1	NM_001145946.2	c.427C>T	p.Pro143Ser	missense_variant	Exon 6 of 16		NP_001139418.1
SLCO1C1	NM_001145945.2	c.427C>T	p.Pro143Ser	missense_variant	Exon 6 of 15		NP_001139417.1
SLCO1C1	NM_001145944.2	c.73C>T	p.Pro25Ser	missense_variant	Exon 3 of 13		NP_001139416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1C1	ENST00000266509.7	c.427C>T	p.Pro143Ser	missense_variant	Exon 5 of 15	1	NM_017435.5	ENSP00000266509.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460618 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 726594

Gnomad4 AFR exome AF: 0.0000299

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: 0.00000720

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.3
DANN	Benign	0.72
DEOGEN2	Benign	0.0048	.;T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.029	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N;N;N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.89	N;N;N;N
REVEL	Benign	0.033
Sift	Benign	0.68	T;T;T;T
Sift4G	Benign	0.95	T;T;T;T
Polyphen		0.0080	.;B;.;.
Vest4		0.13
MutPred		0.41		Gain of catalytic residue at S144 (P = 8e-04);Gain of catalytic residue at S144 (P = 8e-04);Gain of catalytic residue at S144 (P = 8e-04);.;
MVP		0.030
ClinPred		0.031	T
GERP RS		-0.11
Varity_R		0.033
gMVP		0.42

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

Other links and lift over

dbSNP: rs36010656; hg19: chr12-20864342;