NM_001386879.1:c.965T>C

Variant names:

• chr12-21297514-A-G
• rs2136379815
• NM_001386879.1:c.965T>C

Variant summary

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

The NM_001386879.1(SLCO1A2):​c.965T>C​(p.Ile322Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,449,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLCO1A2 NM_001386879.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.73
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30488944).

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.965T>C	p.Ile322Thr	missense	Exon 9 of 15	NP_001373808.1	P46721-1
	SLCO1A2	NM_001386878.1		c.965T>C	p.Ile322Thr	missense	Exon 9 of 15	NP_001373807.1	P46721-1
	SLCO1A2	NM_001386880.1		c.965T>C	p.Ile322Thr	missense	Exon 9 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.965T>C	p.Ile322Thr	missense	Exon 9 of 15	ENSP00000508235.1	P46721-1
	SLCO1A2	ENST00000307378.10	TSL:1	c.965T>C	p.Ile322Thr	missense	Exon 10 of 16	ENSP00000305974.6	P46721-1
	SLCO1A2	ENST00000544020.5	TSL:1	n.*544T>C		non_coding_transcript_exon	Exon 8 of 14	ENSP00000440154.1	F5GXY6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1449546 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 721082

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33130

American (AMR) AF: 0.00 AC: 0 AN: 44176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25740

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39416

South Asian (SAS) AF: 0.00 AC: 0 AN: 84770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103824

Other (OTH) AF: 0.00 AC: 0 AN: 59776

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.076
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.7
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.081
Sift	Benign	0.058	T
Sift4G	Uncertain	0.011	D
Polyphen		0.041	B
Vest4		0.32
MutPred		0.48		Gain of catalytic residue at V324 (P = 0.0041)
MVP		0.36
MPC		0.049
ClinPred		0.85	D
GERP RS		4.0
Varity_R		0.16
gMVP		0.16
Mutation Taster		=57/43	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: rs2136379815; hg19: chr12-21450448; COSMIC: COSV56602610;