chr3-133935789-T-A

Position:

• chr3-133935789-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005630.3(SLCO2A1):​c.1799A>T​(p.Asp600Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D600N) has been classified 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: 3.39

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO2A1	NM_005630.3	c.1799A>T	p.Asp600Val	missense_variant	13/14	ENST00000310926.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO2A1	ENST00000310926.11	c.1799A>T	p.Asp600Val	missense_variant	13/14	1	NM_005630.3	P1
SLCO2A1	ENST00000493729.5	c.1571A>T	p.Asp524Val	missense_variant	12/13	5
SLCO2A1	ENST00000481359.3	c.*361A>T		3_prime_UTR_variant, NMD_transcript_variant	12/13	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 24, 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with SLCO2A1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 600 of the SLCO2A1 protein (p.Asp600Val). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Benign	0.69
DEOGEN2	Benign	0.32	T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.21	N
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	0.80	D;D
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.13	T;D
Polyphen		0.78	P;P
Vest4		0.69
MutPred		0.60		Gain of methylation at R603 (P = 0.0558);.;
MVP		0.64
MPC		0.40
ClinPred		0.85	D
GERP RS		5.4
Varity_R		0.49
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-133654633;