chr15-92162768-C-T

Position:

• chr15-92162768-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_013272.4(SLCO3A1):​c.1766C>T​(p.Pro589Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLCO3A1 NM_013272.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.38

Genes affected

SLCO3A1 (HGNC:10952): (solute carrier organic anion transporter family member 3A1) Predicted to enable sodium-independent organic anion transmembrane transporter activity. Involved in positive regulation of NF-kappaB transcription factor activity; positive regulation of protein phosphorylation; and prostaglandin transport. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.789

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO3A1	NM_013272.4	c.1766C>T	p.Pro589Leu	missense_variant	10/10	ENST00000318445.11	NP_037404.2
SLCO3A1	NM_001145044.1	c.1766C>T	p.Pro589Leu	missense_variant	10/11		NP_001138516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO3A1	ENST00000318445.11	c.1766C>T	p.Pro589Leu	missense_variant	10/10	1	NM_013272.4	ENSP00000320634	P1
	ENST00000561674.1	n.186-5527G>A		intron_variant, non_coding_transcript_variant		1
	ENST00000557683.1			downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2023

The c.1766C>T (p.P589L) alteration is located in exon 10 (coding exon 10) of the SLCO3A1 gene. This alteration results from a C to T substitution at nucleotide position 1766, causing the proline (P) at amino acid position 589 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Uncertain	2.0	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.4	N;N
REVEL	Pathogenic	0.67
Sift	Benign	0.035	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.97	D;D
Vest4		0.76
MutPred		0.67		Loss of catalytic residue at P588 (P = 0.0466);Loss of catalytic residue at P588 (P = 0.0466);
MVP		0.60
MPC		1.1
ClinPred		0.82	D
GERP RS		5.8
Varity_R		0.38
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr15-92705998;