chr12-20715141-T-A

Variant names:

• chr12-20715141-T-A
• NM_017435.5:c.532T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017435.5(SLCO1C1):​c.532T>A​(p.Cys178Ser) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLCO1C1 NM_017435.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.64

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1C1	NM_017435.5	c.532T>A	p.Cys178Ser	missense_variant, splice_region_variant	Exon 6 of 15	ENST00000266509.7	NP_059131.1
SLCO1C1	NM_001145946.2	c.532T>A	p.Cys178Ser	missense_variant, splice_region_variant	Exon 7 of 16		NP_001139418.1
SLCO1C1	NM_001145944.2	c.178T>A	p.Cys60Ser	missense_variant, splice_region_variant	Exon 4 of 13		NP_001139416.1
SLCO1C1	NM_001145945.2	c.530-1991T>A		intron_variant	Intron 6 of 14		NP_001139417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1C1	ENST00000266509.7	c.532T>A	p.Cys178Ser	missense_variant, splice_region_variant	Exon 6 of 15	1	NM_017435.5	ENSP00000266509.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461524 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727028

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

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	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.7	M;M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-7.6	D;D;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.60
MutPred		0.69		Gain of disorder (P = 0.0064);Gain of disorder (P = 0.0064);.;
MVP		0.55
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.84
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.46		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.46		Position offset: 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: chr12-20868075;