3-133947365-C-T

Variant names:

• chr3-133947365-C-T
• rs34550074
• NM_005630.3:c.1186G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 44 publications found

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 Gene-Disease associations (from GenCC):

• hypertrophic osteoarthropathy, primary, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Ambry Genetics
• hypertrophic osteoarthropathy, primary, autosomal recessive, 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• inflammatory bowel disease

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• chronic enteropathy associated with SLCO2A1 gene

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• pachydermoperiostosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1241442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005630.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO2A1	NM_005630.3	MANE Select	c.1186G>A	p.Ala396Thr	missense	Exon 9 of 14	NP_005621.2	Q92959

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO2A1	ENST00000310926.11	TSL:1 MANE Select	c.1186G>A	p.Ala396Thr	missense	Exon 9 of 14	ENSP00000311291.4	Q92959
	SLCO2A1	ENST00000860072.1		c.1225G>A	p.Ala409Thr	missense	Exon 9 of 14	ENSP00000530131.1
	SLCO2A1	ENST00000860067.1		c.1216G>A	p.Ala406Thr	missense	Exon 9 of 14	ENSP00000530126.1

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

GnomAD2 exomes AF: 0.238 AC: 59840 AN: 251174 AF XY: 0.227

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 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

African (AFR) AF: 0.408 AC: 13665 AN: 33466

American (AMR) AF: 0.342 AC: 15266 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5693 AN: 26134

East Asian (EAS) AF: 0.225 AC: 8926 AN: 39692

South Asian (SAS) AF: 0.193 AC: 16648 AN: 86236

European-Finnish (FIN) AF: 0.221 AC: 11828 AN: 53408

Middle Eastern (MID) AF: 0.177 AC: 1020 AN: 5768

European-Non Finnish (NFE) AF: 0.195 AC: 216750 AN: 1111862

Other (OTH) AF: 0.208 AC: 12565 AN: 60392

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

African (AFR) AF: 0.404 AC: 16696 AN: 41376

American (AMR) AF: 0.280 AC: 4282 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3472

East Asian (EAS) AF: 0.257 AC: 1324 AN: 5148

South Asian (SAS) AF: 0.202 AC: 971 AN: 4814

European-Finnish (FIN) AF: 0.238 AC: 2513 AN: 10570

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13541 AN: 67968

Other (OTH) AF: 0.260 AC: 546 AN: 2104

Alfa AF: 0.227 Hom.: 10831

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.027	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.47	N
PhyloP100		0.51
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.054
Sift	Benign	0.77	T
Sift4G	Benign	0.89	T
Polyphen		0.0010	B
Vest4		0.058
MPC		0.10
ClinPred		0.0012	T
GERP RS		4.5
Varity_R		0.054
gMVP		0.40
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

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