5-141929624-C-T

Variant names:

• chr5-141929624-C-T
• rs201186658
• NM_014773.5:c.455C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 14/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.067248434).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014773.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DELE1	NM_014773.5	MANE Select	c.455C>T	p.Pro152Leu	missense	Exon 5 of 12	NP_055588.3
	DELE1	NM_001142603.3		c.455C>T	p.Pro152Leu	missense	Exon 5 of 13	NP_001136075.1	Q14154

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DELE1	ENST00000432126.7	TSL:1 MANE Select	c.455C>T	p.Pro152Leu	missense	Exon 5 of 12	ENSP00000396225.2	Q14154
	DELE1	ENST00000959462.1		c.455C>T	p.Pro152Leu	missense	Exon 5 of 13	ENSP00000629521.1
	DELE1	ENST00000959463.1		c.509C>T	p.Pro170Leu	missense	Exon 5 of 12	ENSP00000629522.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152164 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.000171 AC: 43 AN: 251298 AF XY: 0.000177

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000246 AC: 11 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.000341 AC: 379 AN: 1112008

Other (OTH) AF: 0.000232 AC: 14 AN: 60390

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152164 Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10 AN XY: 74330

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000147 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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.013
Eigen_PC	Benign	-0.087
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.099
Sift	Benign	0.14	T
Sift4G	Uncertain	0.018	D
Polyphen		0.96	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
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs201186658; hg19: chr5-141309189;