Genetic Variant SLCO4A1:p.Phe114Leu (chr20-62656796-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016354.4(SLCO4A1):c.342C>A(p.Phe114Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SLCO4A1
NM_016354.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54

Variant links:

Genes affected

SLCO4A1 (HGNC:10953): (solute carrier organic anion transporter family member 4A1) Predicted to enable sodium-independent organic anion transmembrane transporter activity and thyroid hormone transmembrane transporter activity. Predicted to be involved in sodium-independent organic anion transport. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLCO4A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
SLCO4A1	NM_016354.4 link	c.342C>A	p.Phe114Leu	missense_variant	Exon 2 of 12	ENST00000217159.6	NP_057438.3	Q96BD0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLCO4A1	ENST00000217159.6 link	c.342C>A	p.Phe114Leu	missense_variant	Exon 2 of 12	1	NM_016354.4	ENSP00000217159.1	Q96BD0-1
SLCO4A1	ENST00000370507.5 link	c.342C>A	p.Phe114Leu	missense_variant	Exon 1 of 11	1		ENSP00000359538.1	Q96BD0-1
SLCO4A1	ENST00000497209.5 link	n.342C>A		non_coding_transcript_exon_variant	Exon 2 of 10	1		ENSP00000434245.1	E1P5H9

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249554

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460568

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726608

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.342C>A (p.F114L) alteration is located in exon 2 (coding exon 1) of the SLCO4A1 gene. This alteration results from a C to A substitution at nucleotide position 342, causing the phenylalanine (F) at amino acid position 114 to be replaced by a leucine (L). 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

Pathogenic

0.86

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Benign

0.91

DEOGEN2

Benign

0.048

T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.83

T;.

M_CAP

Benign

0.078

MetaRNN

Uncertain

0.69

D;D

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

L;L

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.31

Sift

Benign

0.87

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.23

B;B

Vest4

0.89

MutPred

0.50

Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);

MVP

0.63

MPC

0.87

ClinPred

0.45

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.32

gMVP

0.83

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