Variant chr3-133934801-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005630.3(SLCO2A1):c.1844C>T(p.Ala615Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,611,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A615A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

SLCO2A1
NM_005630.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.286

Variant links:

Genes affected

SLCO2A1 (HGNC:10955): (solute carrier organic anion transporter family member 2A1) This gene encodes a prostaglandin transporter that is a member of the 12-membrane-spanning superfamily of transporters. The encoded protein may be involved in mediating the uptake and clearance of prostaglandins in numerous tissues. [provided by RefSeq, Dec 2011]

SLCO2A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03752148).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO2A1	NM_005630.3 linkuse as main transcript	c.1844C>T	p.Ala615Val	missense_variant	14/14	ENST00000310926.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLCO2A1	ENST00000310926.11 linkuse as main transcript	c.1844C>T	p.Ala615Val	missense_variant	14/14	1	NM_005630.3	P1
SLCO2A1	ENST00000493729.5 linkuse as main transcript	c.1616C>T	p.Ala539Val	missense_variant	13/13	5
SLCO2A1	ENST00000481359.3 linkuse as main transcript	c.*406C>T		3_prime_UTR_variant, NMD_transcript_variant	13/13	5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152006

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:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000444

AC:

AN:

247524

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

134100

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000411

AC:

AN:

1459900

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

726298

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152006

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74240

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:

0.0000147

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 23, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLCO2A1 protein function. ClinVar contains an entry for this variant (Variation ID: 1396796). This variant has not been reported in the literature in individuals affected with SLCO2A1-related conditions. This variant is present in population databases (rs148426132, gnomAD 0.03%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 615 of the SLCO2A1 protein (p.Ala615Val). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.69

CADD

Benign

8.7

DANN

Benign

0.78

DEOGEN2

Benign

0.054

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.57

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.39

N;N

REVEL

Benign

0.073

Sift

Benign

0.89

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.020

MVP

0.29

MPC

0.11

ClinPred

0.0085

GERP RS

-0.87

Varity_R

0.028

gMVP

0.45

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