chr18-45641293-G-A
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_007163.4(SLC14A2):c.1076G>A(p.Gly359Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SLC14A2
NM_007163.4 missense
NM_007163.4 missense
Scores
10
4
4
Clinical Significance
Conservation
PhyloP100: 9.60
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 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, 0.965
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC14A2 | NM_007163.4 | c.1076G>A | p.Gly359Asp | missense_variant | 8/20 | ENST00000255226.11 | |
LOC105372093 | XR_935423.3 | n.873-4136C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC14A2 | ENST00000255226.11 | c.1076G>A | p.Gly359Asp | missense_variant | 8/20 | 1 | NM_007163.4 | P1 | |
SLC14A2 | ENST00000586448.5 | c.1076G>A | p.Gly359Asp | missense_variant | 9/21 | 2 | P1 | ||
SLC14A2 | ENST00000323329.3 | c.*398G>A | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152226Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251426Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135886
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461858Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727240
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74366
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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 | Jun 07, 2024 | The c.1076G>A (p.G359D) alteration is located in exon 8 (coding exon 7) of the SLC14A2 gene. This alteration results from a G to A substitution at nucleotide position 1076, causing the glycine (G) at amino acid position 359 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
.;N
REVEL
Uncertain
Sift
Uncertain
.;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP
MPC
0.45
ClinPred
D
GERP RS
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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