3-133947365-C-T

Position:

• chr3-133947365-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005630.3(SLCO2A1):​c.1186G>A​(p.Ala396Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,572 control chromosomes in the GnomAD database, including 39,192 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.27 (6106 hom., cov: 31)
  • Exomes 𝑓: 0.21 (33086 hom.)
• Consequence: SLCO2A1 NM_005630.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.511

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037408173).
• BP6: Variant 3-133947365-C-T is Benign according to our data. Variant chr3-133947365-C-T is described in ClinVar as [Benign]. Clinvar id is 1241442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-133947365-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO2A1	NM_005630.3	c.1186G>A	p.Ala396Thr	missense_variant	9/14	ENST00000310926.11	NP_005621.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO2A1	ENST00000310926.11	c.1186G>A	p.Ala396Thr	missense_variant	9/14	1	NM_005630.3	ENSP00000311291.4
SLCO2A1	ENST00000493729.5	c.958G>A	p.Ala320Thr	missense_variant	8/13	5		ENSP00000418893.1
SLCO2A1	ENST00000462770.5	n.766G>A		non_coding_transcript_exon_variant	5/7	2
SLCO2A1	ENST00000481359.3	n.1105+1171G>A		intron_variant		5		ENSP00000420028.3

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40867 AN: 151818 Hom.: 6085 Cov.: 31

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.261

GnomAD3 exomes AF: 0.238 AC: 59840 AN: 251174 Hom.: 7832 AF XY: 0.227 AC XY: 30869 AN XY: 135756

Gnomad AFR exome AF: 0.412

Gnomad AMR exome AF: 0.352

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.252

Gnomad SAS exome AF: 0.192

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.207 AC: 302361 AN: 1461636 Hom.: 33086 Cov.: 34 AF XY: 0.205 AC XY: 149146 AN XY: 727118

Gnomad4 AFR exome AF: 0.408

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.269 AC: 40926 AN: 151936 Hom.: 6106 Cov.: 31 AF XY: 0.270 AC XY: 20059 AN XY: 74268

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.260

Alfa AF: 0.212 Hom.: 5916

Bravo AF: 0.278

TwinsUK AF: 0.192 AC: 712

ALSPAC AF: 0.202 AC: 778

ESP6500AA AF: 0.410 AC: 1807

ESP6500EA AF: 0.187 AC: 1608

ExAC AF: 0.234 AC: 28383

Asia WGS AF: 0.234 AC: 812 AN: 3478

EpiCase AF: 0.185

EpiControl AF: 0.184

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 28783044) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.26
DEOGEN2	Benign	0.062	T;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.027	T;T
MetaRNN	Benign	0.0037	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.47	N;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.52	N;N
REVEL	Benign	0.054
Sift	Benign	0.77	T;T
Sift4G	Benign	0.89	T;T
Polyphen		0.0010	B;B
Vest4		0.058
MPC		0.10
ClinPred		0.0012	T
GERP RS		4.5
Varity_R		0.054
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs34550074; hg19: chr3-133666209; COSMIC: COSV60484378; COSMIC: COSV60484378;