12-21297407-T-G

Position:

• chr12-21297407-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001386879.1(SLCO1A2):​c.1072A>C​(p.Met358Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLCO1A2 NM_001386879.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.54

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.210336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1A2	NM_001386879.1	c.1072A>C	p.Met358Leu	missense_variant	9/15	ENST00000683939.1	NP_001373808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1A2	ENST00000683939.1	c.1072A>C	p.Met358Leu	missense_variant	9/15		NM_001386879.1	ENSP00000508235.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 29, 2024

The c.1072A>C (p.M358L) alteration is located in exon 8 (coding exon 8) of the SLCO1A2 gene. This alteration results from a A to C substitution at nucleotide position 1072, causing the methionine (M) at amino acid position 358 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Benign	0.76
DEOGEN2	Benign	0.045	T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.050	N;N
REVEL	Benign	0.10
Sift	Benign	0.21	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0	B;.
Vest4		0.18
MutPred		0.51		Gain of catalytic residue at L363 (P = 0);.;
MVP		0.39
MPC		0.036
ClinPred		0.32	T
GERP RS		3.9
Varity_R		0.17
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-21450341;