Genetic Variant SLCO4C1:p.Ala499Val (chr5-102249762-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_180991.5(SLCO4C1):c.1496C>T(p.Ala499Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,462 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A499D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLCO4C1
NM_180991.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.15

Publications

6 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO4C1	NM_180991.5 link	c.1496C>T	p.Ala499Val	missense_variant	Exon 9 of 13	ENST00000310954.7	NP_851322.3	Q6ZQN7
SLCO4C1	XM_011543370.3 link	c.1232C>T	p.Ala411Val	missense_variant	Exon 8 of 12		XP_011541672.1
SLCO4C1	XM_011543372.2 link	c.1082C>T	p.Ala361Val	missense_variant	Exon 11 of 15		XP_011541674.1
SLCO4C1	XM_047417146.1 link	c.1082C>T	p.Ala361Val	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.1496C>T	p.Ala499Val	missense_variant	Exon 9 of 13	1	NM_180991.5	ENSP00000309741.6		Q6ZQN7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461462

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727018

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111808

Other (OTH)

AF:

0.00

AC:

AN:

60374

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.78

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.62

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.6

PhyloP100

5.2

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.27

Sift

Benign

0.033

Sift4G

Uncertain

0.018

Polyphen

0.84

Vest4

0.35

MutPred

0.75

Gain of loop (P = 0.1069);

MVP

0.62

MPC

0.063

ClinPred

0.98

GERP RS

4.9

Varity_R

0.27

gMVP

0.58

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr5-102249762-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over