18-63362793-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_002035.4(KDSR):c.184G>A(p.Val62Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000416 in 1,612,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
KDSR
NM_002035.4 missense
NM_002035.4 missense
Scores
3
11
Clinical Significance
Conservation
PhyloP100: 5.61
Genes affected
KDSR (HGNC:4021): (3-ketodihydrosphingosine reductase) The protein encoded by this gene catalyzes the reduction of 3-ketodihydrosphingosine to dihydrosphingosine. The putative active site residues of the encoded protein are found on the cytosolic side of the endoplasmic reticulum membrane. A chromosomal rearrangement involving this gene is a cause of follicular lymphoma, also known as type II chronic lymphatic leukemia. The mutation of a conserved residue in the bovine ortholog causes spinal muscular atrophy. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM1
?
In a topological_domain Cytoplasmic (size 244) in uniprot entity KDSR_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_002035.4
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.27349555).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDSR | NM_002035.4 | c.184G>A | p.Val62Ile | missense_variant | 2/10 | ENST00000645214.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDSR | ENST00000645214.2 | c.184G>A | p.Val62Ile | missense_variant | 2/10 | NM_002035.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152188Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
5
AN:
152188
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250822Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135570
GnomAD3 exomes
AF:
AC:
6
AN:
250822
Hom.:
AF XY:
AC XY:
4
AN XY:
135570
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000425 AC: 62AN: 1459842Hom.: 0 Cov.: 28 AF XY: 0.0000592 AC XY: 43AN XY: 726288
GnomAD4 exome
AF:
AC:
62
AN:
1459842
Hom.:
Cov.:
28
AF XY:
AC XY:
43
AN XY:
726288
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74350
GnomAD4 genome
?
AF:
AC:
5
AN:
152188
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74350
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 24, 2023 | The c.184G>A (p.V62I) alteration is located in exon 2 (coding exon 2) of the KDSR gene. This alteration results from a G to A substitution at nucleotide position 184, causing the valine (V) at amino acid position 62 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
Benign
DEOGEN2
Uncertain
T;T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;N;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Polyphen
B;B;.;.;.
Vest4
0.21, 0.24
MutPred
Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP
0.91
MPC
0.25
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at