5-102257178-A-C

Position:

• chr5-102257178-A-C

Variant summary

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

The NM_180991.5(SLCO4C1):​c.1406T>G​(p.Phe469Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,662 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO4C1	NM_180991.5	c.1406T>G	p.Phe469Cys	missense_variant	8/13	ENST00000310954.7	NP_851322.3
SLCO4C1	XM_011543370.3	c.1142T>G	p.Phe381Cys	missense_variant	7/12		XP_011541672.1
SLCO4C1	XM_011543372.2	c.992T>G	p.Phe331Cys	missense_variant	10/15		XP_011541674.1
SLCO4C1	XM_047417146.1	c.992T>G	p.Phe331Cys	missense_variant	10/15		XP_047273102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO4C1	ENST00000310954.7	c.1406T>G	p.Phe469Cys	missense_variant	8/13	1	NM_180991.5	ENSP00000309741	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455662 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724048

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

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 08, 2024

The c.1406T>G (p.F469C) alteration is located in exon 8 (coding exon 8) of the SLCO4C1 gene. This alteration results from a T to G substitution at nucleotide position 1406, causing the phenylalanine (F) at amino acid position 469 to be replaced by a cysteine (C). 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	0.12
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	0.56	D
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.33
Sift	Benign	0.083	T
Sift4G	Benign	0.21	T
Polyphen		0.011	B
Vest4		0.58
MutPred		0.54		Gain of sheet (P = 0.0028);
MVP		0.66
MPC		0.30
ClinPred		0.90	D
GERP RS		3.4
Varity_R		0.11
gMVP		0.55

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: chr5-101592882;