chr12-21274584-C-A

Variant names:

• chr12-21274584-C-A
• rs1360657527
• NM_001386879.1:c.1678G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001386879.1(SLCO1A2):​c.1678G>T​(p.Gly560Cys) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. G560S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLCO1A2 NM_001386879.1 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.19
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.902

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.1678G>T	p.Gly560Cys	missense splice_region	Exon 14 of 15	NP_001373808.1	P46721-1
	SLCO1A2	NM_001386878.1		c.1678G>T	p.Gly560Cys	missense splice_region	Exon 14 of 15	NP_001373807.1	P46721-1
	SLCO1A2	NM_001386880.1		c.1678G>T	p.Gly560Cys	missense splice_region	Exon 14 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.1678G>T	p.Gly560Cys	missense splice_region	Exon 14 of 15	ENSP00000508235.1	P46721-1
	SLCO1A2	ENST00000307378.10	TSL:1	c.1678G>T	p.Gly560Cys	missense splice_region	Exon 15 of 16	ENSP00000305974.6	P46721-1
	SLCO1A2	ENST00000544020.5	TSL:1	n.*1257G>T		splice_region non_coding_transcript_exon	Exon 13 of 14	ENSP00000440154.1	F5GXY6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.059	D
MutationAssessor	Pathogenic	3.7	H
PhyloP100		6.2
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-8.9	D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.65		Gain of catalytic residue at A563 (P = 0.0012)
MVP		0.76
MPC		0.28
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.95
gMVP		0.72
Mutation Taster		=32/68	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1360657527; hg19: chr12-21427518; COSMIC: COSV100261518; COSMIC: COSV100261518;