15-91916287-G-A

Variant names:

• chr15-91916287-G-A
• rs376852333
• NM_013272.4:c.475G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013272.4(SLCO3A1):​c.475G>A​(p.Glu159Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000514 in 1,555,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E159Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: SLCO3A1 NM_013272.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0799301).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013272.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO3A1	NM_013272.4	MANE Select	c.475G>A	p.Glu159Lys	missense	Exon 2 of 10	NP_037404.2	Q9UIG8-1
	SLCO3A1	NM_001145044.1		c.475G>A	p.Glu159Lys	missense	Exon 2 of 11	NP_001138516.1	Q9UIG8-2
	SLCO3A1	NR_135775.2		n.402G>A		non_coding_transcript_exon	Exon 2 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO3A1	ENST00000318445.11	TSL:1 MANE Select	c.475G>A	p.Glu159Lys	missense	Exon 2 of 10	ENSP00000320634.6	Q9UIG8-1
	SLCO3A1	ENST00000424469.2	TSL:1	c.475G>A	p.Glu159Lys	missense	Exon 2 of 11	ENSP00000387846.2	Q9UIG8-2
	SLCO3A1	ENST00000555769.5	TSL:1	n.370G>A		non_coding_transcript_exon	Exon 2 of 11

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000648 AC: 1 AN: 154266 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000402

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000428 AC: 6 AN: 1403290 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 693610

African (AFR) AF: 0.0000628 AC: 2 AN: 31834

American (AMR) AF: 0.0000277 AC: 1 AN: 36060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25276

East Asian (EAS) AF: 0.0000277 AC: 1 AN: 36060

South Asian (SAS) AF: 0.00 AC: 0 AN: 80588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1084572

Other (OTH) AF: 0.00 AC: 0 AN: 58306

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74316

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.53	N
PhyloP100		1.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.065
Sift	Benign	0.67	T
Sift4G	Benign	0.61	T
Polyphen		0.0070	B
Vest4		0.23
MutPred		0.36		Gain of ubiquitination at E159 (P = 0.0031)
MVP		0.23
MPC		1.3
ClinPred		0.026	T
GERP RS		1.8
Varity_R		0.052
gMVP		0.53
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs376852333; hg19: chr15-92459517; COSMIC: COSV59224463;