NM_180991.5:c.2018T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_180991.5(SLCO4C1):​c.2018T>C​(p.Val673Ala) 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. 13/22 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)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SLCO4C1
NM_180991.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09

Publications

0 publications found
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11945015).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLCO4C1NM_180991.5 linkc.2018T>C p.Val673Ala missense_variant Exon 13 of 13 ENST00000310954.7 NP_851322.3 Q6ZQN7
SLCO4C1XM_011543370.3 linkc.1754T>C p.Val585Ala missense_variant Exon 12 of 12 XP_011541672.1
SLCO4C1XM_011543372.2 linkc.1604T>C p.Val535Ala missense_variant Exon 15 of 15 XP_011541674.1
SLCO4C1XM_047417146.1 linkc.1604T>C p.Val535Ala missense_variant Exon 15 of 15 XP_047273102.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLCO4C1ENST00000310954.7 linkc.2018T>C p.Val673Ala missense_variant Exon 13 of 13 1 NM_180991.5 ENSP00000309741.6 Q6ZQN7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1429380
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
709502
African (AFR)
AF:
0.00
AC:
0
AN:
31860
American (AMR)
AF:
0.00
AC:
0
AN:
36952
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25202
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39234
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79086
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
50062
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5446
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1102290
Other (OTH)
AF:
0.00
AC:
0
AN:
59248
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
Jan 26, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.2018T>C (p.V673A) alteration is located in exon 13 (coding exon 13) of the SLCO4C1 gene. This alteration results from a T to C substitution at nucleotide position 2018, causing the valine (V) at amino acid position 673 to be replaced by an alanine (A). 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
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.036
T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M
PhyloP100
3.1
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.083
Sift
Benign
0.24
T
Sift4G
Benign
0.32
T
Polyphen
0.0040
B
Vest4
0.078
MutPred
0.48
Loss of ubiquitination at K676 (P = 0.1441);
MVP
0.24
MPC
0.049
ClinPred
0.55
D
GERP RS
4.1
Varity_R
0.088
gMVP
0.27
Mutation Taster
=77/23
polymorphism

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

Other links and lift over

dbSNP: rs756998819; hg19: chr5-101572719; API