18-45734389-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015865.7(SLC14A1):ā€‹c.457A>Gā€‹(p.Met153Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.000042 ( 0 hom. )

Consequence

SLC14A1
NM_015865.7 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.849
Variant links:
Genes affected
SLC14A1 (HGNC:10918): (solute carrier family 14 member 1 (Kidd blood group)) The protein encoded by this gene is a membrane transporter that mediates urea transport in erythrocytes. This gene forms the basis for the Kidd blood group system. [provided by RefSeq, Mar 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17391834).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC14A1NM_015865.7 linkc.457A>G p.Met153Val missense_variant Exon 5 of 10 ENST00000321925.9 NP_056949.4 Q13336-1G0W2N5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC14A1ENST00000321925.9 linkc.457A>G p.Met153Val missense_variant Exon 5 of 10 1 NM_015865.7 ENSP00000318546.4 Q13336-1

Frequencies

GnomAD3 genomes
AF:
0.0000264
AC:
4
AN:
151702
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000589
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251478
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000424
AC:
62
AN:
1461564
Hom.:
0
Cov.:
32
AF XY:
0.0000454
AC XY:
33
AN XY:
727090
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.0000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000264
AC:
4
AN:
151702
Hom.:
0
Cov.:
32
AF XY:
0.0000270
AC XY:
2
AN XY:
74024
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000589
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000675
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.457A>G (p.M153V) alteration is located in exon 5 (coding exon 3) of the SLC14A1 gene. This alteration results from a A to G substitution at nucleotide position 457, causing the methionine (M) at amino acid position 153 to be replaced by a valine (V). 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
0.068
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
12
DANN
Benign
0.78
DEOGEN2
Benign
0.096
T;T;T;.;.;T;.;.;.;.;T;T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.76
.;T;T;.;.;.;T;T;T;T;T;.
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.17
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;.;.;.;.;L;.;.;.;.;L;.
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-2.1
N;.;N;N;.;.;N;N;N;.;.;.
REVEL
Benign
0.077
Sift
Benign
0.26
T;.;T;T;.;.;T;T;T;.;.;.
Sift4G
Benign
0.25
T;T;T;T;T;.;T;T;T;T;T;T
Polyphen
0.0020
B;.;B;B;.;B;.;.;B;.;B;.
Vest4
0.14
MutPred
0.61
Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);.;.;.;Gain of sheet (P = 0.0344);.;.;.;.;Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP
0.40
MPC
0.11
ClinPred
0.040
T
GERP RS
3.1
Varity_R
0.64
gMVP
0.90

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: rs779936392; hg19: chr18-43314354; API