chr12-21269733-C-T

Variant names:

• chr12-21269733-C-T
• rs747899567
• NM_001386879.1:c.1828G>A

Variant summary

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

The NM_001386879.1(SLCO1A2):​c.1828G>A​(p.Gly610Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,611,584 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: SLCO1A2 NM_001386879.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54
• Publications: 2 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 0 ACMG points.

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.1828G>A	p.Gly610Arg	missense	Exon 15 of 15	NP_001373808.1	P46721-1
	SLCO1A2	NM_001386878.1		c.1828G>A	p.Gly610Arg	missense	Exon 15 of 15	NP_001373807.1	P46721-1
	SLCO1A2	NM_001386880.1		c.1828G>A	p.Gly610Arg	missense	Exon 15 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.1828G>A	p.Gly610Arg	missense	Exon 15 of 15	ENSP00000508235.1	P46721-1
	SLCO1A2	ENST00000307378.10	TSL:1	c.1828G>A	p.Gly610Arg	missense	Exon 16 of 16	ENSP00000305974.6	P46721-1
	SLCO1A2	ENST00000544020.5	TSL:1	n.*1407G>A		non_coding_transcript_exon	Exon 14 of 14	ENSP00000440154.1	F5GXY6

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151788 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000480 AC: 12 AN: 250128 AF XY: 0.0000518

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000974

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000438 AC: 64 AN: 1459796 Hom.: 0 Cov.: 31 AF XY: 0.0000482 AC XY: 35 AN XY: 726128

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39610

South Asian (SAS) AF: 0.0000465 AC: 4 AN: 86012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5756

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1110730

Other (OTH) AF: 0.0000332 AC: 2 AN: 60276

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151788 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74130

African (AFR) AF: 0.00 AC: 0 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67818

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000676 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000548

EpiControl AF: 0.000178

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	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.27
Sift	Benign	0.076	T
Sift4G	Benign	0.17	T
Polyphen		0.98	D
Vest4		0.70
MutPred		0.59		Gain of catalytic residue at V614 (P = 8e-04)
MVP		0.62
MPC		0.23
ClinPred		0.92	D
GERP RS		4.9
Varity_R		0.28
gMVP		0.65
Mutation Taster		=65/35	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: rs747899567; hg19: chr12-21422667;