12-20711408-C-A

Variant names:

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

Variant summary

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

The NM_017435.5(SLCO1C1):​c.427C>A​(p.Pro143Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,610,402 control chromosomes in the GnomAD database, including 1,860 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.034 (126 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1734 hom.)
• Consequence: SLCO1C1 NM_017435.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 15 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 (MetaRNN=0.0017707348).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1C1	NM_017435.5	c.427C>A	p.Pro143Thr	missense_variant	Exon 5 of 15	ENST00000266509.7	NP_059131.1
SLCO1C1	NM_001145946.2	c.427C>A	p.Pro143Thr	missense_variant	Exon 6 of 16		NP_001139418.1
SLCO1C1	NM_001145945.2	c.427C>A	p.Pro143Thr	missense_variant	Exon 6 of 15		NP_001139417.1
SLCO1C1	NM_001145944.2	c.73C>A	p.Pro25Thr	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>A	p.Pro143Thr	missense_variant	Exon 5 of 15	1	NM_017435.5	ENSP00000266509.2

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5250 AN: 152172 Hom.: 126 Cov.: 32

Gnomad AFR AF: 0.00963

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.0518

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0516

GnomAD2 exomes AF: 0.0340 AC: 8523 AN: 250724 AF XY: 0.0348

Gnomad AFR exome AF: 0.0100

Gnomad AMR exome AF: 0.0331

Gnomad ASJ exome AF: 0.0522

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0148

Gnomad NFE exome AF: 0.0520

Gnomad OTH exome AF: 0.0387

GnomAD4 exome AF: 0.0446 AC: 65096 AN: 1458112 Hom.: 1734 Cov.: 30 AF XY: 0.0443 AC XY: 32164 AN XY: 725480

African (AFR) AF: 0.00777 AC: 260 AN: 33446

American (AMR) AF: 0.0352 AC: 1572 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.0546 AC: 1424 AN: 26096

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39666

South Asian (SAS) AF: 0.00827 AC: 712 AN: 86054

European-Finnish (FIN) AF: 0.0155 AC: 827 AN: 53362

Middle Eastern (MID) AF: 0.0301 AC: 173 AN: 5756

European-Non Finnish (NFE) AF: 0.0521 AC: 57735 AN: 1108832

Other (OTH) AF: 0.0396 AC: 2388 AN: 60274

GnomAD4 genome AF: 0.0345 AC: 5247 AN: 152290 Hom.: 126 Cov.: 32 AF XY: 0.0322 AC XY: 2398 AN XY: 74460

African (AFR) AF: 0.00960 AC: 399 AN: 41558

American (AMR) AF: 0.0516 AC: 790 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0518 AC: 180 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.00684 AC: 33 AN: 4822

European-Finnish (FIN) AF: 0.0126 AC: 134 AN: 10606

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0527 AC: 3584 AN: 68026

Other (OTH) AF: 0.0501 AC: 106 AN: 2114

Alfa AF: 0.0457 Hom.: 425

Bravo AF: 0.0382

TwinsUK AF: 0.0523 AC: 194

ALSPAC AF: 0.0586 AC: 226

ESP6500AA AF: 0.00953 AC: 42

ESP6500EA AF: 0.0552 AC: 475

ExAC AF: 0.0328 AC: 3983

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.0556

EpiControl AF: 0.0610

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.6
DANN	Benign	0.86
DEOGEN2	Benign	0.0044	.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.85	T;D;D;D
MetaRNN	Benign	0.0018	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;N;N;.
PhyloP100		0.015
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.82	N;N;N;N
REVEL	Benign	0.034
Sift	Benign	0.53	T;T;T;T
Sift4G	Benign	0.78	T;T;T;T
Polyphen		0.022	.;B;.;.
Vest4		0.18
ClinPred		0.0012	T
GERP RS		-0.11
Varity_R		0.048
gMVP		0.47
Mutation Taster		=97/3	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: rs36010656; hg19: chr12-20864342; COSMIC: COSV56881108;