3-133934772-T-A

Variant names:

• chr3-133934772-T-A
• NM_005630.3:c.1873A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005630.3(SLCO2A1):​c.1873A>T​(p.Ser625Cys) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLCO2A1 NM_005630.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.288
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27222824).

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.1873A>T	p.Ser625Cys	missense	Exon 14 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.1873A>T	p.Ser625Cys	missense	Exon 14 of 14	ENSP00000311291.4	Q92959
	SLCO2A1	ENST00000860072.1		c.1912A>T	p.Ser638Cys	missense	Exon 14 of 14	ENSP00000530131.1
	SLCO2A1	ENST00000860067.1		c.1903A>T	p.Ser635Cys	missense	Exon 14 of 14	ENSP00000530126.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.29
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Benign	0.19	T
Sift4G	Benign	0.13	T
Polyphen		0.98	D
Vest4		0.22
MutPred		0.56		Gain of catalytic residue at W626 (P = 0.0168)
MVP		0.63
MPC		0.11
ClinPred		0.72	D
GERP RS		3.4
Varity_R		0.084
gMVP		0.79
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

hg19: chr3-133653616;