chr18-45663887-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_007163.4(SLC14A2):c.1454C>G(p.Ser485Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,136 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SLC14A2
NM_007163.4 missense
NM_007163.4 missense
Scores
7
8
Clinical Significance
Conservation
PhyloP100: 2.21
Genes affected
SLC14A2 (HGNC:10919): (solute carrier family 14 member 2) The protein encoded by this gene belongs to the urea transporter family. In mammalian cells, urea is the chief end product of nitrogen catabolism, and plays an important role in the urinary concentration mechanism. This protein is expressed in the inner medulla of the kidney, and mediates rapid transepithelial urea transport across the inner medullary collecting duct. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
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 | UniProt |
---|---|---|---|---|---|---|---|
SLC14A2 | NM_007163.4 | c.1454C>G | p.Ser485Cys | missense_variant | 11/20 | ENST00000255226.11 | |
LOC105372093 | XR_935423.3 | n.873-26730G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC14A2 | ENST00000255226.11 | c.1454C>G | p.Ser485Cys | missense_variant | 11/20 | 1 | NM_007163.4 | P1 | |
SLC14A2 | ENST00000586448.5 | c.1454C>G | p.Ser485Cys | missense_variant | 12/21 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152042Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460976Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726766
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74392
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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 submitter | clinical testing | Ambry Genetics | Feb 21, 2024 | The c.1454C>G (p.S485C) alteration is located in exon 11 (coding exon 10) of the SLC14A2 gene. This alteration results from a C to G substitution at nucleotide position 1454, causing the serine (S) at amino acid position 485 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of disorder (P = 0.0194);Loss of disorder (P = 0.0194);
MVP
MPC
0.20
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at