5-141929672-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014773.5(DELE1):​c.503C>T​(p.Ser168Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

DELE1
NM_014773.5 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.171
Variant links:
Genes affected
DELE1 (HGNC:28969): (DAP3 binding cell death enhancer 1) Enables protein kinase binding activity and protein serine/threonine kinase activator activity. Involved in HRI-mediated signaling; extrinsic apoptotic signaling pathway via death domain receptors; and regulation of cysteine-type endopeptidase activity involved in apoptotic process. Located in cytosol and mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07443023).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DELE1NM_014773.5 linkc.503C>T p.Ser168Leu missense_variant Exon 5 of 12 ENST00000432126.7 NP_055588.3 Q14154

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DELE1ENST00000432126.7 linkc.503C>T p.Ser168Leu missense_variant Exon 5 of 12 1 NM_014773.5 ENSP00000396225.2 Q14154
DELE1ENST00000194118.8 linkc.503C>T p.Ser168Leu missense_variant Exon 5 of 13 5 ENSP00000194118.4 Q14154
DELE1ENST00000508751.1 linkc.503C>T p.Ser168Leu missense_variant Exon 5 of 9 5 ENSP00000422686.1 D6RBI8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 22, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.503C>T (p.S168L) alteration is located in exon 5 (coding exon 5) of the KIAA0141 gene. This alteration results from a C to T substitution at nucleotide position 503, causing the serine (S) at amino acid position 168 to be replaced by a leucine (L). 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
0.087
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Benign
0.0049
T;T;T
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.046
N
LIST_S2
Benign
0.66
.;T;T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.074
T;T;T
MetaSVM
Benign
-0.98
T
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.7
N;N;N
REVEL
Benign
0.023
Sift
Benign
0.14
T;T;T
Sift4G
Benign
0.28
T;T;T
Polyphen
0.0010
B;B;.
Vest4
0.12
MutPred
0.25
Gain of catalytic residue at S168 (P = 0.0323);Gain of catalytic residue at S168 (P = 0.0323);Gain of catalytic residue at S168 (P = 0.0323);
MVP
0.20
MPC
0.15
ClinPred
0.082
T
GERP RS
-0.83
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.055
gMVP
0.26

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: chr5-141309237; API