5-102239304-C-T

Variant names:

• chr5-102239304-C-T
• NM_180991.5:c.1961G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_180991.5(SLCO4C1):​c.1961G>A​(p.Gly654Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 5.59

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO4C1	NM_180991.5	c.1961G>A	p.Gly654Glu	missense_variant	Exon 12 of 13	ENST00000310954.7	NP_851322.3
SLCO4C1	XM_011543370.3	c.1697G>A	p.Gly566Glu	missense_variant	Exon 11 of 12		XP_011541672.1
SLCO4C1	XM_011543372.2	c.1547G>A	p.Gly516Glu	missense_variant	Exon 14 of 15		XP_011541674.1
SLCO4C1	XM_047417146.1	c.1547G>A	p.Gly516Glu	missense_variant	Exon 14 of 15		XP_047273102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO4C1	ENST00000310954.7	c.1961G>A	p.Gly654Glu	missense_variant	Exon 12 of 13	1	NM_180991.5	ENSP00000309741.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1961G>A (p.G654E) alteration is located in exon 12 (coding exon 12) of the SLCO4C1 gene. This alteration results from a G to A substitution at nucleotide position 1961, causing the glycine (G) at amino acid position 654 to be replaced by a glutamic acid (E). 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	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	-0.036	T
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.067	T
Polyphen		0.97	D
Vest4		0.97
MutPred		0.90		Loss of sheet (P = 0.0817);
MVP		0.68
MPC		0.33
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.93
gMVP		0.86

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: chr5-101575008; COSMIC: COSV60517570;