3-133947365-C-G

Position:

• chr3-133947365-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005630.3(SLCO2A1):​c.1186G>C​(p.Ala396Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A396T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLCO2A1 NM_005630.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3904618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO2A1	NM_005630.3	c.1186G>C	p.Ala396Pro	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>C	p.Ala396Pro	missense_variant	9/14	1	NM_005630.3	ENSP00000311291.4
SLCO2A1	ENST00000493729.5	c.958G>C	p.Ala320Pro	missense_variant	8/13	5		ENSP00000418893.1
SLCO2A1	ENST00000462770.5	n.766G>C		non_coding_transcript_exon_variant	5/7	2
SLCO2A1	ENST00000481359.3	n.1105+1171G>C		intron_variant		5		ENSP00000420028.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.31	T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.13
Sift	Benign	0.33	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.90	P;P
Vest4		0.44
MutPred		0.65		Loss of helix (P = 0.079);.;
MVP		0.64
MPC		0.27
ClinPred		0.58	D
GERP RS		4.5
Varity_R		0.44
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;