rs752611378
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The NM_002035.4(KDSR):c.879G>A(p.Gln293=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.0000647 in 1,607,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000069 ( 0 hom. )
Consequence
KDSR
NM_002035.4 splice_region, synonymous
NM_002035.4 splice_region, synonymous
Scores
2
Splicing: ADA: 0.5912
2
Clinical Significance
Conservation
PhyloP100: 6.12
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 18-63335257-C-T is Pathogenic according to our data. Variant chr18-63335257-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 427791.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.3). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDSR | NM_002035.4 | c.879G>A | p.Gln293= | splice_region_variant, synonymous_variant | 9/10 | ENST00000645214.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDSR | ENST00000645214.2 | c.879G>A | p.Gln293= | splice_region_variant, synonymous_variant | 9/10 | NM_002035.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250812Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135570
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GnomAD4 exome AF: 0.0000687 AC: 100AN: 1455310Hom.: 0 Cov.: 28 AF XY: 0.0000663 AC XY: 48AN XY: 724478
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74356
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Erythrokeratodermia variabilis et progressiva 4 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 13, 2017 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at