Variant chr5-102260274-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_180991.5(SLCO4C1):c.1067G>A(p.Ser356Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000642 in 1,246,092 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 0.0000064 ( 1 hom. )

Consequence

SLCO4C1
NM_180991.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.490

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023178726).

BP6

Variant 5-102260274-C-T is Benign according to our data. Variant chr5-102260274-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2315229.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLCO4C1	NM_180991.5 linkuse as main transcript	c.1067G>A	p.Ser356Asn	missense_variant	6/13	ENST00000310954.7	NP_851322.3
SLCO4C1	XM_011543370.3 linkuse as main transcript	c.803G>A	p.Ser268Asn	missense_variant	5/12		XP_011541672.1
SLCO4C1	XM_011543372.2 linkuse as main transcript	c.653G>A	p.Ser218Asn	missense_variant	8/15		XP_011541674.1
SLCO4C1	XM_047417146.1 linkuse as main transcript	c.653G>A	p.Ser218Asn	missense_variant	8/15		XP_047273102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO4C1	ENST00000310954.7 linkuse as main transcript	c.1067G>A	p.Ser356Asn	missense_variant	6/13	1	NM_180991.5	ENSP00000309741	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000445

AC:

AN:

179944

Hom.:

AF XY:

0.0000404

AC XY:

AN XY:

99064

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000303

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000529

GnomAD4 exome

AF:

0.00000642

AC:

AN:

1246092

Hom.:

Cov.:

AF XY:

0.00000653

AC XY:

AN XY:

612786

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000245

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:

0.00000100

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.018

DANN

Benign

0.31

DEOGEN2

Benign

0.0061

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0081

LIST_S2

Benign

0.36

M_CAP

Benign

0.0064

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.41

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

0.43

REVEL

Benign

0.020

Sift

Benign

0.54

Sift4G

Benign

0.49

Polyphen

0.0

Vest4

0.093

MutPred

0.39

Loss of loop (P = 0.0203);

MVP

0.085

MPC

0.040

ClinPred

0.024

GERP RS

-6.3

Varity_R

0.035

gMVP

0.17

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

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