NM_180991.5:c.1514G>A

Variant names:

• chr5-102249744-C-T
• rs141775272
• NM_180991.5:c.1514G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_180991.5(SLCO4C1):​c.1514G>A​(p.Cys505Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C505F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: SLCO4C1 NM_180991.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.77
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.948

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO4C1	NM_180991.5	c.1514G>A	p.Cys505Tyr	missense_variant	Exon 9 of 13	ENST00000310954.7	NP_851322.3
SLCO4C1	XM_011543370.3	c.1250G>A	p.Cys417Tyr	missense_variant	Exon 8 of 12		XP_011541672.1
SLCO4C1	XM_011543372.2	c.1100G>A	p.Cys367Tyr	missense_variant	Exon 11 of 15		XP_011541674.1
SLCO4C1	XM_047417146.1	c.1100G>A	p.Cys367Tyr	missense_variant	Exon 11 of 15		XP_047273102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO4C1	ENST00000310954.7	c.1514G>A	p.Cys505Tyr	missense_variant	Exon 9 of 13	1	NM_180991.5	ENSP00000309741.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000192 AC: 28 AN: 1461646 Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12 AN XY: 727120

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111882

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.084	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		3.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-10	D
REVEL	Uncertain	0.58
Sift	Benign	0.079	T
Sift4G	Benign	0.061	T
Polyphen		1.0	D
Vest4		0.98
MutPred		0.70		Gain of helix (P = 0.132);
MVP		0.70
MPC		0.36
ClinPred		1.0	D
GERP RS		3.8
Varity_R		0.60
gMVP		0.92
Mutation Taster		=37/63	disease causing

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: rs141775272; hg19: chr5-101585448;