chr18-45734331-G-A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The ENST00000535474.5(SLC14A1):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
SLC14A1
ENST00000535474.5 start_lost
ENST00000535474.5 start_lost
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 2.07
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC14A1 | NM_015865.7 | c.399G>A | p.Met133Ile | missense_variant | 5/10 | ENST00000321925.9 | |
LOC105372093 | XR_935423.3 | n.826+3135C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC14A1 | ENST00000321925.9 | c.399G>A | p.Met133Ile | missense_variant | 5/10 | 1 | NM_015865.7 | P1 | |
ENST00000589510.5 | n.160+3135C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251468Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135906
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461852Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727232
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74286
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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 | Apr 12, 2023 | The c.399G>A (p.M133I) alteration is located in exon 5 (coding exon 3) of the SLC14A1 gene. This alteration results from a G to A substitution at nucleotide position 399, causing the methionine (M) at amino acid position 133 to be replaced by an isoleucine (I). 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;.;T;.;.;T;.;.;.;.;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.;.;L;.;.;.;.;.;L;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;D;D;.;.;D;D;.;D;.;.;.
REVEL
Benign
Sift
Benign
T;.;.;T;T;.;.;T;T;.;T;.;.;.
Sift4G
Benign
T;T;D;T;T;T;.;T;T;T;T;T;T;T
Polyphen
B;.;.;B;B;.;B;.;.;.;B;.;B;.
Vest4
MutPred
Loss of catalytic residue at M133 (P = 0.0393);Loss of catalytic residue at M133 (P = 0.0393);.;.;.;.;Loss of catalytic residue at M133 (P = 0.0393);.;.;Loss of catalytic residue at M133 (P = 0.0393);.;.;Loss of catalytic residue at M133 (P = 0.0393);Loss of catalytic residue at M133 (P = 0.0393);
MVP
MPC
0.12
ClinPred
T
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