chr18-45625824-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007163.4(SLC14A2):​c.292C>A​(p.Leu98Ile) 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. 15/21 in silico tools predict a benign 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. L98F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SLC14A2
NM_007163.4 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0650
Variant links:
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_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.061927557).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC14A2NM_007163.4 linkc.292C>A p.Leu98Ile missense_variant Exon 3 of 20 ENST00000255226.11 NP_009094.3 Q15849-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC14A2ENST00000255226.11 linkc.292C>A p.Leu98Ile missense_variant Exon 3 of 20 1 NM_007163.4 ENSP00000255226.5 Q15849-1
SLC14A2ENST00000586448.5 linkc.292C>A p.Leu98Ile missense_variant Exon 4 of 21 2 ENSP00000465953.1 Q15849-1
SLC14A2ENST00000323329.3 linkn.292C>A non_coding_transcript_exon_variant Exon 3 of 11 2 ENSP00000320689.3 E7EPU1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000568
AC:
1
AN:
175970
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
97316
show subpopulations
Gnomad AFR exome
AF:
0.0000881
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1356920
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
668854
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
7.4
DANN
Benign
0.78
DEOGEN2
Benign
0.16
T;T
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.60
FATHMM_MKL
Benign
0.47
N
M_CAP
Benign
0.0073
T
MetaRNN
Benign
0.062
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;L
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.020
.;N
REVEL
Benign
0.017
Sift
Benign
0.59
.;T
Sift4G
Benign
0.33
T;T
Polyphen
0.0010
B;B
Vest4
0.21
MutPred
0.24
Gain of catalytic residue at L98 (P = 0.0067);Gain of catalytic residue at L98 (P = 0.0067);
MVP
0.26
MPC
0.070
ClinPred
0.10
T
GERP RS
2.6
Varity_R
0.039
gMVP
0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148670019; hg19: chr18-43205789; API