5-141923955-C-T

Variant names:

• chr5-141923955-C-T
• rs761762806
• NM_014773.5:c.14C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014773.5(DELE1):​c.14C>T​(p.Pro5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,609,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: DELE1 NM_014773.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33
• 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]

ENSG00000306969 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07391924).

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.14C>T	p.Pro5Leu	missense	Exon 1 of 12	NP_055588.3
	DELE1	NM_001142603.3		c.14C>T	p.Pro5Leu	missense	Exon 1 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.14C>T	p.Pro5Leu	missense	Exon 1 of 12	ENSP00000396225.2	Q14154
	DELE1	ENST00000959462.1		c.14C>T	p.Pro5Leu	missense	Exon 1 of 13	ENSP00000629521.1
	DELE1	ENST00000959463.1		c.14C>T	p.Pro5Leu	missense	Exon 1 of 12	ENSP00000629522.1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000209 AC: 5 AN: 238682 AF XY: 0.00000771

Gnomad AFR exome AF: 0.0000676

Gnomad AMR exome AF: 0.0000894

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000172

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1456868 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724326

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.0000682 AC: 3 AN: 44004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25982

East Asian (EAS) AF: 0.00 AC: 0 AN: 39492

South Asian (SAS) AF: 0.00 AC: 0 AN: 85242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110032

Other (OTH) AF: 0.0000333 AC: 2 AN: 60128

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74376

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.000262 AC: 4 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68044

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

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.00000824 AC: 1

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	0.17
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.020
Sift	Benign	0.065	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.28	B
Vest4		0.25
MutPred		0.33		Loss of catalytic residue at P5 (P = 0.0058)
MVP		0.41
MPC		0.17
ClinPred		0.53	D
GERP RS		3.7
PromoterAI		-0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.077
gMVP		0.26
Mutation Taster		=95/5	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: rs761762806; hg19: chr5-141303520;