chr12-20701395-G-C

Variant names:

• chr12-20701395-G-C
• rs1351615984
• NM_017435.5:c.207G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017435.5(SLCO1C1):​c.207G>C​(p.Gln69His) 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 pathogenic 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: 2.17

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.889

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1C1	NM_017435.5	c.207G>C	p.Gln69His	missense_variant	Exon 3 of 15	ENST00000266509.7	NP_059131.1
SLCO1C1	NM_001145946.2	c.207G>C	p.Gln69His	missense_variant	Exon 4 of 16		NP_001139418.1
SLCO1C1	NM_001145945.2	c.207G>C	p.Gln69His	missense_variant	Exon 4 of 15		NP_001139417.1
SLCO1C1	NM_001145944.2	c.-83-4554G>C		intron_variant	Intron 1 of 12		NP_001139416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1C1	ENST00000266509.7	c.207G>C	p.Gln69His	missense_variant	Exon 3 of 15	1	NM_017435.5	ENSP00000266509.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.207G>C (p.Q69H) alteration is located in exon 4 (coding exon 2) of the SLCO1C1 gene. This alteration results from a G to C substitution at nucleotide position 207, causing the glutamine (Q) at amino acid position 69 to be replaced by a histidine (H). 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	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	.;T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.77	T;D;T
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.89	D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.7	M;M;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Uncertain	0.36
Sift	Benign	0.087	T;T;T
Sift4G	Uncertain	0.022	D;D;D
Polyphen		0.93	.;P;.
Vest4		0.88
MutPred		0.74		Gain of catalytic residue at I67 (P = 0.0321);Gain of catalytic residue at I67 (P = 0.0321);Gain of catalytic residue at I67 (P = 0.0321);
MVP		0.56
ClinPred		0.99	D
GERP RS		2.0
Varity_R		0.37
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1351615984; hg19: chr12-20854329; COSMIC: COSV56875094; COSMIC: COSV56875094;