15-92104393-A-G

Position:

• chr15-92104393-A-G

Variant summary

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

The NM_013272.4(SLCO3A1):​c.860A>G​(p.Gln287Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLCO3A1 NM_013272.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.63

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]

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
SLCO3A1	NM_013272.4	c.860A>G	p.Gln287Arg	missense_variant	4/10	ENST00000318445.11
SLCO3A1	NM_001145044.1	c.860A>G	p.Gln287Arg	missense_variant	4/11
SLCO3A1	NR_135775.2	n.787A>G		non_coding_transcript_exon_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO3A1	ENST00000318445.11	c.860A>G	p.Gln287Arg	missense_variant	4/10	1	NM_013272.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Apr 24, 2024

The c.860A>G (p.Q287R) alteration is located in exon 4 (coding exon 4) of the SLCO3A1 gene. This alteration results from a A to G substitution at nucleotide position 860, causing the glutamine (Q) at amino acid position 287 to be replaced by an arginine (R). 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	Benign	0.082
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.18	N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.62	N;N
REVEL	Benign	0.22
Sift	Benign	0.19	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.0090	B;P
Vest4		0.74
MutPred		0.44		Gain of glycosylation at P286 (P = 0.0884);Gain of glycosylation at P286 (P = 0.0884);
MVP		0.48
MPC		0.44
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.28
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.31		Position offset: 21

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1596104989; hg19: chr15-92647623;