Variant 5-102438651-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173488.5(SLCO6A1):c.1242T>G(p.Phe414Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000188 in 1,591,728 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

SLCO6A1
NM_173488.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59

Variant links:

Genes affected

SLCO6A1 (HGNC:23613): (solute carrier organic anion transporter family member 6A1) Predicted to enable sodium-independent organic anion 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 membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLCO6A1 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/exons	MANE	Protein	UniProt
SLCO6A1	NM_173488.5 linkuse as main transcript	c.1242T>G	p.Phe414Leu	missense_variant	7/14	ENST00000506729.6	NP_775759.3	Q86UG4-1A0A140VJU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO6A1	ENST00000506729.6 linkuse as main transcript	c.1242T>G	p.Phe414Leu	missense_variant	7/14	1	NM_173488.5	ENSP00000421339.1		Q86UG4-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000260

AC:

AN:

230384

Hom.:

AF XY:

0.00000800

AC XY:

AN XY:

125016

show subpopulations

Gnomad AFR exome

AF:

0.000387

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000625

AC:

AN:

1439696

Hom.:

Cov.:

AF XY:

0.00000559

AC XY:

AN XY:

715678

show subpopulations

Gnomad4 AFR exome

AF:

0.000248

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:

0.00

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.000138

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.000507

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000988

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

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

Jul 14, 2024

The c.1242T>G (p.F414L) alteration is located in exon 7 (coding exon 7) of the SLCO6A1 gene. This alteration results from a T to G substitution at nucleotide position 1242, causing the phenylalanine (F) at amino acid position 414 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

0.97

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;T;.

Eigen

Benign

0.052

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.73

.;T;T

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.7

M;M;.

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.4

D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.014

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.60

MutPred

0.81

Gain of glycosylation at T419 (P = 0.147);Gain of glycosylation at T419 (P = 0.147);.;

MVP

0.22

MPC

0.57

ClinPred

0.71

GERP RS

2.1

Varity_R

0.65

gMVP

0.51

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