Genetic Variant NM_180991.5:c.1523C>T (chr5-102249735-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_180991.5(SLCO4C1):c.1523C>T(p.Ser508Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

SLCO4C1
NM_180991.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.16

Publications

3 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012419194).

BP6

Variant 5-102249735-G-A is Benign according to our data. Variant chr5-102249735-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3320389.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO4C1	NM_180991.5 link	c.1523C>T	p.Ser508Leu	missense_variant	Exon 9 of 13	ENST00000310954.7	NP_851322.3	Q6ZQN7
SLCO4C1	XM_011543370.3 link	c.1259C>T	p.Ser420Leu	missense_variant	Exon 8 of 12		XP_011541672.1
SLCO4C1	XM_011543372.2 link	c.1109C>T	p.Ser370Leu	missense_variant	Exon 11 of 15		XP_011541674.1
SLCO4C1	XM_047417146.1 link	c.1109C>T	p.Ser370Leu	missense_variant	Exon 11 of 15		XP_047273102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO4C1	ENST00000310954.7 link	c.1523C>T	p.Ser508Leu	missense_variant	Exon 9 of 13	1	NM_180991.5	ENSP00000309741.6		Q6ZQN7

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000749

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000638

AC:

AN:

250860

AF XY:

0.0000885

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461634

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33470

American (AMR)

AF:

0.000157

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111882

Other (OTH)

AF:

0.0000166

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000210

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41530

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00193

Hom.:

Bravo

AF:

0.000253

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

May 20, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

0.065

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.014

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.23

M_CAP

Benign

0.0065

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.10

PhyloP100

1.2

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.11

REVEL

Benign

0.077

Sift

Benign

0.92

Sift4G

Benign

0.41

Polyphen

0.0030

Vest4

0.15

MVP

0.14

MPC

0.039

ClinPred

0.0096

GERP RS

4.5

Varity_R

0.040

gMVP

0.33

Mutation Taster

=96/4

polymorphism

(source)

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

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NM_180991.5:c.1523C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over