Variant 5-102239281-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_180991.5(SLCO4C1):c.1984A>T(p.Ile662Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,374 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLCO4C1
NM_180991.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.555

Variant links:

Genes affected

SLCO4C1 (HGNC:23612): (solute carrier organic anion transporter family member 4C1) SLCO4C1 belongs to the organic anion transporter (OATP) family. OATPs are involved in the membrane transport of bile acids, conjugated steroids, thyroid hormone, eicosanoids, peptides, and numerous drugs in many tissues (Mikkaichi et al., 2004 [PubMed 14993604]).[supplied by OMIM, Mar 2008]

SLCO4C1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.123351246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLCO4C1	NM_180991.5 linkuse as main transcript	c.1984A>T	p.Ile662Phe	missense_variant	12/13	ENST00000310954.7	NP_851322.3
SLCO4C1	XM_011543370.3 linkuse as main transcript	c.1720A>T	p.Ile574Phe	missense_variant	11/12		XP_011541672.1
SLCO4C1	XM_011543372.2 linkuse as main transcript	c.1570A>T	p.Ile524Phe	missense_variant	14/15		XP_011541674.1
SLCO4C1	XM_047417146.1 linkuse as main transcript	c.1570A>T	p.Ile524Phe	missense_variant	14/15		XP_047273102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO4C1	ENST00000310954.7 linkuse as main transcript	c.1984A>T	p.Ile662Phe	missense_variant	12/13	1	NM_180991.5	ENSP00000309741	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1448374

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.1984A>T (p.I662F) alteration is located in exon 12 (coding exon 12) of the SLCO4C1 gene. This alteration results from a A to T substitution at nucleotide position 1984, causing the isoleucine (I) at amino acid position 662 to be replaced by a phenylalanine (F). 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

Benign

0.085

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.48

DEOGEN2

Benign

0.012

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.66

M_CAP

Benign

0.0080

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

MutationTaster

Benign

0.62

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.81

REVEL

Benign

0.10

Sift

Benign

0.71

Sift4G

Benign

0.72

Polyphen

0.0020

Vest4

0.40

MutPred

0.40

Loss of sheet (P = 0.1501);

MVP

0.30

MPC

0.060

ClinPred

0.26

GERP RS

4.3

Varity_R

0.056

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over