chr15-92162863-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013272.4(SLCO3A1):​c.1861G>A​(p.Val621Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.000019 ( 0 hom. )

Consequence

SLCO3A1
NM_013272.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14172179).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLCO3A1NM_013272.4 linkuse as main transcriptc.1861G>A p.Val621Ile missense_variant 10/10 ENST00000318445.11 NP_037404.2
SLCO3A1NM_001145044.1 linkuse as main transcriptc.1861G>A p.Val621Ile missense_variant 10/11 NP_001138516.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLCO3A1ENST00000318445.11 linkuse as main transcriptc.1861G>A p.Val621Ile missense_variant 10/101 NM_013272.4 ENSP00000320634 P1Q9UIG8-1
ENST00000557683.1 linkuse as main transcriptn.474C>T non_coding_transcript_exon_variant 2/24
ENST00000561674.1 linkuse as main transcriptn.186-5622C>T intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251478
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1461894
Hom.:
0
Cov.:
30
AF XY:
0.0000179
AC XY:
13
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000234
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000370
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsJan 29, 2024The c.1861G>A (p.V621I) alteration is located in exon 10 (coding exon 10) of the SLCO3A1 gene. This alteration results from a G to A substitution at nucleotide position 1861, causing the valine (V) at amino acid position 621 to be replaced by an isoleucine (I). 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
0.071
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.073
T;.
Eigen
Benign
-0.19
Eigen_PC
Benign
0.00069
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.58
N;N
MutationTaster
Benign
0.67
D;D;D
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.41
N;N
REVEL
Benign
0.052
Sift
Benign
0.18
T;T
Sift4G
Benign
0.11
T;T
Polyphen
0.0
B;B
Vest4
0.054
MVP
0.21
MPC
0.31
ClinPred
0.40
T
GERP RS
4.4
Varity_R
0.086
gMVP
0.50

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.

Other links and lift over

dbSNP: rs764695708; hg19: chr15-92706093; API