Variant 15-92126247-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_013272.4(SLCO3A1):c.1361C>A(p.Pro454His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SLCO3A1
NM_013272.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.85

Variant links:

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]

SLCO3A1 links:

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ACMG classification

Classification made for transcript

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=0.33076546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLCO3A1	NM_013272.4 linkuse as main transcript	c.1361C>A	p.Pro454His	missense_variant	6/10	ENST00000318445.11
SLCO3A1	NM_001145044.1 linkuse as main transcript	c.1361C>A	p.Pro454His	missense_variant	6/11
SLCO3A1	NR_135775.2 linkuse as main transcript	n.1288C>A		non_coding_transcript_exon_variant	6/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO3A1	ENST00000318445.11 linkuse as main transcript	c.1361C>A	p.Pro454His	missense_variant	6/10	1	NM_013272.4	P1	Q9UIG8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.1361C>A (p.P454H) alteration is located in exon 6 (coding exon 6) of the SLCO3A1 gene. This alteration results from a C to A substitution at nucleotide position 1361, causing the proline (P) at amino acid position 454 to be replaced by a histidine (H). 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

0.14

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.083

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.036

D;D

Polyphen

0.095

B;P

Vest4

0.59

MutPred

0.45

Gain of catalytic residue at P454 (P = 0.044);Gain of catalytic residue at P454 (P = 0.044);

MVP

0.043

MPC

1.1

ClinPred

0.95

GERP RS

4.5

Varity_R

0.52

gMVP

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over