chr12-21295706-C-A

Variant names:

• chr12-21295706-C-A
• rs894763906
• NM_001386879.1:c.1162G>T

Variant summary

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

The NM_001386879.1(SLCO1A2):​c.1162G>T​(p.Ala388Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,456,392 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A388T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: SLCO1A2 NM_001386879.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.31
• Publications: 0 publications found

Genes affected

SLCO1A2 (HGNC:10956): (solute carrier organic anion transporter family member 1A2) This gene encodes a sodium-independent transporter which mediates cellular uptake of organic ions in the liver. Its substrates include bile acids, bromosulphophthalein, and some steroidal compounds. The protein is a member of the SLC21A family of solute carriers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386879.1. 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
	SLCO1A2	NM_001386879.1	MANE Select	c.1162G>T	p.Ala388Ser	missense	Exon 10 of 15	NP_001373808.1	P46721-1
	SLCO1A2	NM_001386878.1		c.1162G>T	p.Ala388Ser	missense	Exon 10 of 15	NP_001373807.1	P46721-1
	SLCO1A2	NM_001386880.1		c.1162G>T	p.Ala388Ser	missense	Exon 10 of 15	NP_001373809.1	P46721-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1A2	ENST00000683939.1	MANE Select	c.1162G>T	p.Ala388Ser	missense	Exon 10 of 15	ENSP00000508235.1	P46721-1
	SLCO1A2	ENST00000307378.10	TSL:1	c.1162G>T	p.Ala388Ser	missense	Exon 11 of 16	ENSP00000305974.6	P46721-1
	SLCO1A2	ENST00000544020.5	TSL:1	n.*741G>T		non_coding_transcript_exon	Exon 9 of 14	ENSP00000440154.1	F5GXY6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1456392 Hom.: 0 Cov.: 28 AF XY: 0.00000828 AC XY: 6 AN XY: 725006

African (AFR) AF: 0.00 AC: 0 AN: 33340

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39538

South Asian (SAS) AF: 0.00 AC: 0 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1107264

Other (OTH) AF: 0.0000166 AC: 1 AN: 60216

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.3
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.28
Sift	Benign	0.056	T
Sift4G	Benign	0.065	T
Polyphen		0.97	D
Vest4		0.45
MutPred		0.67		Gain of catalytic residue at W393 (P = 0)
MVP		0.57
MPC		0.27
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.53
gMVP		0.40
Mutation Taster		=54/46	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: rs894763906; hg19: chr12-21448640;