15-92126247-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

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=0.35333598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO3A1	NM_013272.4	c.1361C>T	p.Pro454Leu	missense_variant	Exon 6 of 10	ENST00000318445.11	NP_037404.2
SLCO3A1	NM_001145044.1	c.1361C>T	p.Pro454Leu	missense_variant	Exon 6 of 11		NP_001138516.1
SLCO3A1	NR_135775.2	n.1288C>T		non_coding_transcript_exon_variant	Exon 6 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO3A1	ENST00000318445.11	c.1361C>T	p.Pro454Leu	missense_variant	Exon 6 of 10	1	NM_013272.4	ENSP00000320634.6

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.1	D;D
REVEL	Benign	0.080
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.053	T;D
Polyphen		0.019	B;B
Vest4		0.62
MutPred		0.50		Loss of disorder (P = 0.0339);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-92669477; COSMIC: COSV59235609;