5-141924586-C-T

Variant names:

• chr5-141924586-C-T
• rs369129396
• NM_014773.5:c.37C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014773.5(DELE1):​c.37C>T​(p.Pro13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000996 in 1,606,310 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000099 (1 hom.)
• Consequence: DELE1 NM_014773.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

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

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=0.089156866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DELE1	NM_014773.5	c.37C>T	p.Pro13Ser	missense_variant	Exon 2 of 12	ENST00000432126.7	NP_055588.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DELE1	ENST00000432126.7	c.37C>T	p.Pro13Ser	missense_variant	Exon 2 of 12	1	NM_014773.5	ENSP00000396225.2
DELE1	ENST00000194118.8	c.37C>T	p.Pro13Ser	missense_variant	Exon 2 of 13	5		ENSP00000194118.4
DELE1	ENST00000508751.1	c.37C>T	p.Pro13Ser	missense_variant	Exon 2 of 9	5		ENSP00000422686.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000179 AC: 45 AN: 251358 Hom.: 0 AF XY: 0.000177 AC XY: 24 AN XY: 135840

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.0000990 AC: 144 AN: 1454162 Hom.: 1 Cov.: 29 AF XY: 0.000116 AC XY: 84 AN XY: 723996

Gnomad4 AFR exome AF: 0.0000600

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000650

Gnomad4 FIN exome AF: 0.000262

Gnomad4 NFE exome AF: 0.0000434

Gnomad4 OTH exome AF: 0.000183

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74330

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.0000364 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000173 AC: 21

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 15, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.37C>T (p.P13S) alteration is located in exon 2 (coding exon 2) of the KIAA0141 gene. This alteration results from a C to T substitution at nucleotide position 37, causing the proline (P) at amino acid position 13 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	0.11
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.70
DEOGEN2	Benign	0.0026	T;T;T
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.038
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.69	.;T;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.80	N;N;N
REVEL	Benign	0.046
Sift	Benign	0.26	T;T;T
Sift4G	Uncertain	0.030	D;D;D
Polyphen		0.73	P;P;.
Vest4		0.25
MVP		0.39
MPC		0.16
ClinPred		0.031	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.070
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs369129396; hg19: chr5-141304151;