5-102257244-C-A

Position:

• chr5-102257244-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_180991.5(SLCO4C1):​c.1340G>T​(p.Arg447Ile) 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. 13/21 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: SLCO4C1 NM_180991.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.41

Genes affected

SLCO4C1 (HGNC:23612): (solute carrier organic anion transporter family member 4C1) SLCO4C1 belongs to the organic anion transporter (OATP) family. OATPs are involved in the membrane transport of bile acids, conjugated steroids, thyroid hormone, eicosanoids, peptides, and numerous drugs in many tissues (Mikkaichi et al., 2004 [PubMed 14993604]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4042696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO4C1	NM_180991.5	c.1340G>T	p.Arg447Ile	missense_variant	8/13	ENST00000310954.7
SLCO4C1	XM_011543370.3	c.1076G>T	p.Arg359Ile	missense_variant	7/12
SLCO4C1	XM_011543372.2	c.926G>T	p.Arg309Ile	missense_variant	10/15
SLCO4C1	XM_047417146.1	c.926G>T	p.Arg309Ile	missense_variant	10/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO4C1	ENST00000310954.7	c.1340G>T	p.Arg447Ile	missense_variant	8/13	1	NM_180991.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Feb 15, 2023

The c.1340G>T (p.R447I) alteration is located in exon 8 (coding exon 8) of the SLCO4C1 gene. This alteration results from a G to T substitution at nucleotide position 1340, causing the arginine (R) at amino acid position 447 to be replaced by an isoleucine (I). 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	0.32
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.028
Eigen_PC	Benign	0.0075
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.82	D
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.54	P
Vest4		0.36
MutPred		0.63		Loss of catalytic residue at R447 (P = 0.0155);
MVP		0.50
MPC		0.13
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.41
gMVP		0.51

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-101592948;