5-141929672-C-T

Variant names:

• chr5-141929672-C-T
• NM_014773.5:c.503C>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.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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.171

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=0.07443023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DELE1	NM_014773.5	c.503C>T	p.Ser168Leu	missense_variant	Exon 5 of 12	ENST00000432126.7	NP_055588.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DELE1	ENST00000432126.7	c.503C>T	p.Ser168Leu	missense_variant	Exon 5 of 12	1	NM_014773.5	ENSP00000396225.2
DELE1	ENST00000194118.8	c.503C>T	p.Ser168Leu	missense_variant	Exon 5 of 13	5		ENSP00000194118.4
DELE1	ENST00000508751.1	c.503C>T	p.Ser168Leu	missense_variant	Exon 5 of 9	5		ENSP00000422686.1

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

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;