18-63362787-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM4PP5_Moderate
The NM_002035.4(KDSR):c.190C>T(p.Arg64Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000497 in 1,609,840 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 Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
KDSR
NM_002035.4 stop_gained
NM_002035.4 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 3.84
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 Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Stoplost variant in NM_002035.4 Downstream stopcodon found after 39 codons.
PP5
?
Variant 18-63362787-G-A is Pathogenic according to our data. Variant chr18-63362787-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3067941.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDSR | NM_002035.4 | c.190C>T | p.Arg64Ter | stop_gained | 2/10 | ENST00000645214.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDSR | ENST00000645214.2 | c.190C>T | p.Arg64Ter | stop_gained | 2/10 | NM_002035.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152128Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
3
AN:
152128
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: 0.00000798 AC: 2AN: 250476Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135432
GnomAD3 exomes
AF:
AC:
2
AN:
250476
Hom.:
AF XY:
AC XY:
1
AN XY:
135432
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: 0.00000343 AC: 5AN: 1457712Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1AN XY: 725360
GnomAD4 exome
AF:
AC:
5
AN:
1457712
Hom.:
Cov.:
28
AF XY:
AC XY:
1
AN XY:
725360
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: 0.0000197 AC: 3AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74296
GnomAD4 genome
?
AF:
AC:
3
AN:
152128
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74296
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:
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
1
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Erythrokeratodermia variabilis et progressiva 4 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Apr 04, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
0.47, 0.47
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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