NM_007256.5:c.440C>A

Variant names:

• chr11-75165941-C-A
• rs561594626
• NM_007256.5:c.440C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007256.5(SLCO2B1):​c.440C>A​(p.Thr147Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLCO2B1 NM_007256.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.529
• Publications: 0 publications found

Genes affected

SLCO2B1 (HGNC:10962): (solute carrier organic anion transporter family member 2B1) This locus encodes a member of the organic anion-transporting polypeptide family of membrane proteins. The protein encoded by this locus may function in regulation of placental uptake of sulfated steroids. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08936262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO2B1	NM_007256.5	c.440C>A	p.Thr147Asn	missense_variant	Exon 4 of 14	ENST00000289575.10	NP_009187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO2B1	ENST00000289575.10	c.440C>A	p.Thr147Asn	missense_variant	Exon 4 of 14	1	NM_007256.5	ENSP00000289575.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 10, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.440C>A (p.T147N) alteration is located in exon 4 (coding exon 4) of the SLCO2B1 gene. This alteration results from a C to A substitution at nucleotide position 440, causing the threonine (T) at amino acid position 147 to be replaced by an asparagine (N). 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	0.079
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.7
DANN	Benign	0.79
DEOGEN2	Benign	0.015	.;T;.;.;.;.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.69	T;T;.;T;T;.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.089	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.53
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;N
REVEL	Benign	0.029
Sift	Benign	0.077	T;T;T;T;T;T;T
Sift4G	Benign	0.21	T;T;T;T;T;T;T
Vest4		0.11
MutPred		0.38		Loss of phosphorylation at T147 (P = 0.0506);.;.;.;.;.;.;
MVP		0.40
MPC		0.27
ClinPred		0.13	T
GERP RS		0.45
PromoterAI		0.011	Neutral
gMVP		0.32
Mutation Taster		=91/9	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: rs561594626; hg19: chr11-74876986; COSMIC: COSV56938685; COSMIC: COSV56938685;