Variant 5-102399556-G-A 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.1813C>T(p.Arg605Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,523,306 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

SLCO6A1
NM_173488.5 missense, splice_region

Scores

Splicing: ADA: 0.0008928

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.277

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:

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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.1813C>T	p.Arg605Trp	missense_variant, splice_region_variant	10/14	ENST00000506729.6	NP_775759.3	Q86UG4-1A0A140VJU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLCO6A1	ENST00000506729.6 linkuse as main transcript	c.1813C>T	p.Arg605Trp	missense_variant, splice_region_variant	10/14	1	NM_173488.5	ENSP00000421339.1	Q86UG4-1
SLCO6A1	ENST00000379807.7 linkuse as main transcript	c.1813C>T	p.Arg605Trp	missense_variant, splice_region_variant	10/14	1		ENSP00000369135.3	Q86UG4-1
SLCO6A1	ENST00000389019.7 linkuse as main transcript	c.1627C>T	p.Arg543Trp	missense_variant, splice_region_variant	9/13	1		ENSP00000373671.3	Q86UG4-2
SLCO6A1	ENST00000513675.1 linkuse as main transcript	c.1054C>T	p.Arg352Trp	missense_variant, splice_region_variant	5/9	2		ENSP00000421990.1	C9J020

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

151768

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:

0.000760

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000167

AC:

AN:

228030

Hom.:

AF XY:

0.000137

AC XY:

AN XY:

124506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000609

Gnomad SAS exome

AF:

0.0000364

Gnomad FIN exome

AF:

0.000430

Gnomad NFE exome

AF:

0.000243

Gnomad OTH exome

AF:

0.000188

GnomAD4 exome

AF:

0.000147

AC:

202

AN:

1371538

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

107

AN XY:

679272

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000517

Gnomad4 SAS exome

AF:

0.0000148

Gnomad4 FIN exome

AF:

0.000321

Gnomad4 NFE exome

AF:

0.000167

Gnomad4 OTH exome

AF:

0.0000890

GnomAD4 genome

AF:

0.000191

AC:

AN:

151768

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

74072

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:

0.000760

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000179

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000989

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

Mar 19, 2024

The c.1813C>T (p.R605W) alteration is located in exon 10 (coding exon 10) of the SLCO6A1 gene. This alteration results from a C to T substitution at nucleotide position 1813, causing the arginine (R) at amino acid position 605 to be replaced by a tryptophan (W). 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;T;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.59

.;T;T;T

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.66

D;D;D;D

MetaSVM

Benign

-0.49

MutationAssessor

Pathogenic

3.3

M;M;.;.

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-6.9

D;D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.77

MVP

0.50

MPC

0.54

ClinPred

0.46

GERP RS

0.28

Varity_R

0.63

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00089

dbscSNV1_RF

Benign

0.064

SpliceAI score (max)

0.060

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