chr5-141929624-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014773.5(DELE1):​c.455C>T​(p.Pro152Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

DELE1
NM_014773.5 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.067248434).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DELE1NM_014773.5 linkc.455C>T p.Pro152Leu 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.455C>T p.Pro152Leu missense_variant Exon 5 of 12 1 NM_014773.5 ENSP00000396225.2 Q14154
DELE1ENST00000194118.8 linkc.455C>T p.Pro152Leu missense_variant Exon 5 of 13 5 ENSP00000194118.4 Q14154
DELE1ENST00000508751.1 linkc.455C>T p.Pro152Leu missense_variant Exon 5 of 9 5 ENSP00000422686.1 D6RBI8

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152164
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000171
AC:
43
AN:
251298
Hom.:
0
AF XY:
0.000177
AC XY:
24
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000229
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000278
AC:
406
AN:
1461842
Hom.:
0
Cov.:
30
AF XY:
0.000268
AC XY:
195
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000246
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000341
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152164
Hom.:
0
Cov.:
33
AF XY:
0.000135
AC XY:
10
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000220
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000179
Hom.:
0
Bravo
AF:
0.0000982
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.000222
AC:
27
EpiCase
AF:
0.000109
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 12, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.455C>T (p.P152L) 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 455, causing the proline (P) at amino acid position 152 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
0.093
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0042
T;T;T
Eigen
Benign
-0.013
Eigen_PC
Benign
-0.087
FATHMM_MKL
Benign
0.63
D
LIST_S2
Benign
0.82
.;T;T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.067
T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-2.1
N;N;N
REVEL
Benign
0.099
Sift
Benign
0.14
T;T;T
Sift4G
Uncertain
0.018
D;D;D
Polyphen
0.96
D;D;.
Vest4
0.39
MVP
0.44
MPC
0.60
ClinPred
0.069
T
GERP RS
5.1
Varity_R
0.069
gMVP
0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201186658; hg19: chr5-141309189; API