5-102257298-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_180991.5(SLCO4C1):​c.1286T>A​(p.Ile429Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

SLCO4C1
NM_180991.5 missense

Scores

9
5
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.68
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.922

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLCO4C1NM_180991.5 linkuse as main transcriptc.1286T>A p.Ile429Asn missense_variant 8/13 ENST00000310954.7 NP_851322.3 Q6ZQN7
SLCO4C1XM_011543370.3 linkuse as main transcriptc.1022T>A p.Ile341Asn missense_variant 7/12 XP_011541672.1
SLCO4C1XM_011543372.2 linkuse as main transcriptc.872T>A p.Ile291Asn missense_variant 10/15 XP_011541674.1
SLCO4C1XM_047417146.1 linkuse as main transcriptc.872T>A p.Ile291Asn missense_variant 10/15 XP_047273102.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLCO4C1ENST00000310954.7 linkuse as main transcriptc.1286T>A p.Ile429Asn missense_variant 8/131 NM_180991.5 ENSP00000309741.6 Q6ZQN7

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 08, 2024The c.1286T>A (p.I429N) alteration is located in exon 8 (coding exon 8) of the SLCO4C1 gene. This alteration results from a T to A substitution at nucleotide position 1286, causing the isoleucine (I) at amino acid position 429 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
Pathogenic
0.97
BayesDel_addAF
Uncertain
0.097
D
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.042
D
MetaRNN
Pathogenic
0.92
D
MetaSVM
Uncertain
-0.0066
T
MutationAssessor
Pathogenic
3.5
H
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-6.2
D
REVEL
Uncertain
0.41
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.91
MutPred
0.77
Loss of catalytic residue at L434 (P = 0.0477);
MVP
0.66
MPC
0.36
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.95
gMVP
0.66

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: chr5-101593002; API