12-20753056-T-C

Variant names:

• chr12-20753056-T-C
• rs10444412
• NM_017435.5:c.*528T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017435.5(SLCO1C1):​c.*528T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,018 control chromosomes in the GnomAD database, including 17,223 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (17222 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: SLCO1C1 NM_017435.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 9 publications found

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]

SLCO1C1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017435.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1C1	NM_017435.5	MANE Select	c.*528T>C		3_prime_UTR	Exon 15 of 15	NP_059131.1	Q9NYB5-1
	SLCO1C1	NM_001145946.2		c.*577T>C		3_prime_UTR	Exon 16 of 16	NP_001139418.1	Q9NYB5-3
	SLCO1C1	NM_001145945.2		c.*528T>C		3_prime_UTR	Exon 15 of 15	NP_001139417.1	Q9NYB5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1C1	ENST00000266509.7	TSL:1 MANE Select	c.*528T>C		3_prime_UTR	Exon 15 of 15	ENSP00000266509.2	Q9NYB5-1
	SLCO1C1	ENST00000947229.1		c.*528T>C		3_prime_UTR	Exon 14 of 14	ENSP00000617288.1
	SLCO1C1	ENST00000545102.1	TSL:2	c.*577T>C		3_prime_UTR	Exon 13 of 13	ENSP00000444527.1	Q9NYB5-4

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69091 AN: 151892 Hom.: 17219 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 3 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.455 AC: 69110 AN: 152012 Hom.: 17222 Cov.: 32 AF XY: 0.458 AC XY: 34016 AN XY: 74300

African (AFR) AF: 0.239 AC: 9895 AN: 41480

American (AMR) AF: 0.548 AC: 8363 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1790 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3084 AN: 5154

South Asian (SAS) AF: 0.592 AC: 2855 AN: 4820

European-Finnish (FIN) AF: 0.484 AC: 5099 AN: 10546

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36358 AN: 67970

Other (OTH) AF: 0.433 AC: 914 AN: 2110

Alfa AF: 0.483 Hom.: 17970

Bravo AF: 0.453

Asia WGS AF: 0.565 AC: 1961 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
DANN	Benign	0.89
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10444412; hg19: chr12-20905990;