Variant chr15-92104419-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013272.4(SLCO3A1):c.886G>A(p.Ala296Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

SLCO3A1
NM_013272.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03207791).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLCO3A1	NM_013272.4 linkuse as main transcript	c.886G>A	p.Ala296Thr	missense_variant	4/10	ENST00000318445.11	NP_037404.2
SLCO3A1	NM_001145044.1 linkuse as main transcript	c.886G>A	p.Ala296Thr	missense_variant	4/11		NP_001138516.1
SLCO3A1	NR_135775.2 linkuse as main transcript	n.813G>A		non_coding_transcript_exon_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO3A1	ENST00000318445.11 linkuse as main transcript	c.886G>A	p.Ala296Thr	missense_variant	4/10	1	NM_013272.4	ENSP00000320634	P1	Q9UIG8-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000716

AC:

AN:

251322

Hom.:

AF XY:

0.0000810

AC XY:

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000494

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

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

Mar 01, 2023

The c.886G>A (p.A296T) alteration is located in exon 4 (coding exon 4) of the SLCO3A1 gene. This alteration results from a G to A substitution at nucleotide position 886, causing the alanine (A) at amino acid position 296 to be replaced by a threonine (T). 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

0.067

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.30

N;N

MutationTaster

Benign

0.85

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.12

Sift

Benign

0.43

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.020

B;B

Vest4

0.054

MVP

0.25

MPC

0.37

ClinPred

0.018

GERP RS

2.0

Varity_R

0.047

gMVP

0.16

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