Variant 5-102419851-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_173488.5(SLCO6A1):c.1447G>T(p.Ala483Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000544 in 1,598,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

SLCO6A1
NM_173488.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO6A1	NM_173488.5 linkuse as main transcript	c.1447G>T	p.Ala483Ser	missense_variant	8/14	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.1447G>T	p.Ala483Ser	missense_variant	8/14	1	NM_173488.5	ENSP00000421339.1	Q86UG4-1
SLCO6A1	ENST00000379807.7 linkuse as main transcript	c.1447G>T	p.Ala483Ser	missense_variant	8/14	1		ENSP00000369135.3	Q86UG4-1
SLCO6A1	ENST00000389019.7 linkuse as main transcript	c.1261G>T	p.Ala421Ser	missense_variant	7/13	1		ENSP00000373671.3	Q86UG4-2
SLCO6A1	ENST00000513675.1 linkuse as main transcript	c.714-6708G>T		intron_variant		2		ENSP00000421990.1	C9J020

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152104

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000598

AC:

AN:

234104

Hom.:

AF XY:

0.0000474

AC XY:

AN XY:

126582

show subpopulations

Gnomad AFR exome

AF:

0.0000644

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:

0.000119

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000553

AC:

AN:

1446534

Hom.:

Cov.:

AF XY:

0.0000570

AC XY:

AN XY:

719178

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:

0.0000695

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74266

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:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000893

Hom.:

Bravo

AF:

0.0000302

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

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

Dec 28, 2023

The c.1447G>T (p.A483S) alteration is located in exon 8 (coding exon 8) of the SLCO6A1 gene. This alteration results from a G to T substitution at nucleotide position 1447, causing the alanine (A) at amino acid position 483 to be replaced by a serine (S). 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

Benign

0.25

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.76

.;T;T

M_CAP

Benign

0.0096

MetaRNN

Pathogenic

0.75

D;D;D

MetaSVM

Benign

-0.53

MutationAssessor

Pathogenic

3.0

M;M;.

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.077

T;T;T

Polyphen

0.98

D;D;D

Vest4

0.66

MVP

0.31

MPC

0.49

ClinPred

0.52

GERP RS

5.0

Varity_R

0.61

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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