NM_013272.4:c.1361C>T

Variant names:

• chr15-92126247-C-T
• rs776746205
• NM_013272.4:c.1361C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013272.4(SLCO3A1):​c.1361C>T​(p.Pro454Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P454H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLCO3A1 NM_013272.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35333598).

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.1361C>T	p.Pro454Leu	missense	Exon 6 of 10	NP_037404.2	Q9UIG8-1
	SLCO3A1	NM_001145044.1		c.1361C>T	p.Pro454Leu	missense	Exon 6 of 11	NP_001138516.1	Q9UIG8-2
	SLCO3A1	NR_135775.2		n.1288C>T		non_coding_transcript_exon	Exon 6 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO3A1	ENST00000318445.11	TSL:1 MANE Select	c.1361C>T	p.Pro454Leu	missense	Exon 6 of 10	ENSP00000320634.6	Q9UIG8-1
	SLCO3A1	ENST00000424469.2	TSL:1	c.1361C>T	p.Pro454Leu	missense	Exon 6 of 11	ENSP00000387846.2	Q9UIG8-2
	SLCO3A1	ENST00000555769.5	TSL:1	n.1256C>T		non_coding_transcript_exon	Exon 6 of 11

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461804 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111944

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.069
Eigen_PC	Benign	0.075
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.9
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.080
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.053	T
Polyphen		0.019	B
Vest4		0.62
MutPred		0.50		Loss of disorder (P = 0.0339)
MVP		0.068
MPC		0.63
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.43
gMVP		0.80
Mutation Taster		=61/39	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: rs776746205; hg19: chr15-92669477; COSMIC: COSV59235609;