Variant 5-102413024-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_173488.5(SLCO6A1):c.1592G>C(p.Gly531Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,144 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: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SLCO6A1
NM_173488.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.25

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.932

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO6A1	NM_173488.5 linkuse as main transcript	c.1592G>C	p.Gly531Ala	missense_variant	9/14	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.1592G>C	p.Gly531Ala	missense_variant	9/14	1	NM_173488.5	ENSP00000421339.1	Q86UG4-1
SLCO6A1	ENST00000379807.7 linkuse as main transcript	c.1592G>C	p.Gly531Ala	missense_variant	9/14	1		ENSP00000369135.3	Q86UG4-1
SLCO6A1	ENST00000389019.7 linkuse as main transcript	c.1406G>C	p.Gly469Ala	missense_variant	8/13	1		ENSP00000373671.3	Q86UG4-2
SLCO6A1	ENST00000513675.1 linkuse as main transcript	c.833G>C	p.Gly278Ala	missense_variant	4/9	2		ENSP00000421990.1	C9J020

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.19e-7

AC:

AN:

1391144

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688898

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:

0.00

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

Cov.:

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

Aug 21, 2023

The c.1592G>C (p.G531A) alteration is located in exon 9 (coding exon 9) of the SLCO6A1 gene. This alteration results from a G to C substitution at nucleotide position 1592, causing the glycine (G) at amino acid position 531 to be replaced by an alanine (A). 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

0.74

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;T;.;.

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.84

.;T;T;D

M_CAP

Benign

0.0063

MetaRNN

Pathogenic

0.93

D;D;D;D

MetaSVM

Benign

-0.84

MutationAssessor

Pathogenic

3.8

H;H;.;.

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.5

D;D;D;D

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.063

T;T;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.64

MutPred

0.84

Gain of catalytic residue at G531 (P = 0.164);Gain of catalytic residue at G531 (P = 0.164);.;.;

MVP

0.33

MPC

0.55

ClinPred

0.99

GERP RS

4.3

Varity_R

0.91

gMVP

0.84

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over