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GeneBe

18-63331895-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002035.4(KDSR):c.886A>T(p.Thr296Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

KDSR
NM_002035.4 missense

Scores

1
5
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.33
Variant links:
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KDSRNM_002035.4 linkuse as main transcriptc.886A>T p.Thr296Ser missense_variant 10/10 ENST00000645214.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KDSRENST00000645214.2 linkuse as main transcriptc.886A>T p.Thr296Ser missense_variant 10/10 NM_002035.4 P1Q06136-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMar 02, 2023The c.886A>T (p.T296S) alteration is located in exon 10 (coding exon 10) of the KDSR gene. This alteration results from a A to T substitution at nucleotide position 886, causing the threonine (T) at amino acid position 296 to be replaced by a serine (S). 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
0.21
BayesDel_addAF
Uncertain
0.077
D
BayesDel_noAF
Benign
-0.13
Cadd
Benign
20
Dann
Uncertain
0.99
DEOGEN2
Benign
0.34
T;T;.;.
Eigen
Benign
0.064
Eigen_PC
Benign
0.16
FATHMM_MKL
Pathogenic
0.97
D
M_CAP
Benign
0.075
D
MetaRNN
Uncertain
0.49
T;T;T;T
MetaSVM
Uncertain
-0.28
T
MutationAssessor
Benign
1.9
L;L;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.62
T
Polyphen
0.56
P;P;.;.
Vest4
0.27, 0.34
MutPred
0.52
Loss of helix (P = 0.028);Loss of helix (P = 0.028);.;.;
MVP
0.94
MPC
0.29
ClinPred
0.86
D
GERP RS
5.5
Varity_R
0.17
gMVP
0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-60999128; API