Genetic Variant NM_014773.5:c.170C>T (chr5-141925433-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014773.5(DELE1):c.170C>T(p.Thr57Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,595,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

DELE1
NM_014773.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.801

Publications

0 publications found

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]

DELE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.073527515).

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.170C>T	p.Thr57Met	missense	Exon 3 of 12	NP_055588.3
	DELE1	NM_001142603.3		c.170C>T	p.Thr57Met	missense	Exon 3 of 13	NP_001136075.1	Q14154

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DELE1	ENST00000432126.7	TSL:1 MANE Select	c.170C>T	p.Thr57Met	missense	Exon 3 of 12	ENSP00000396225.2	Q14154
DELE1	ENST00000959462.1		c.170C>T	p.Thr57Met	missense	Exon 3 of 13	ENSP00000629521.1
DELE1	ENST00000959463.1		c.170C>T	p.Thr57Met	missense	Exon 3 of 12	ENSP00000629522.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000128

AC:

AN:

234910

AF XY:

0.00000785

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000180

AC:

AN:

1443688

Hom.:

Cov.:

AF XY:

0.0000223

AC XY:

AN XY:

718050

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32240

American (AMR)

AF:

0.0000237

AC:

AN:

42126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25634

East Asian (EAS)

AF:

0.00

AC:

AN:

37888

South Asian (SAS)

AF:

0.0000119

AC:

AN:

83694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53168

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000190

AC:

AN:

1103552

Other (OTH)

AF:

0.0000503

AC:

AN:

59672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000566

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0061

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.73

M_CAP

Benign

0.016

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.0

PhyloP100

0.80

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.77

REVEL

Benign

0.10

Sift

Benign

0.098

Sift4G

Benign

0.11

Polyphen

0.78

Vest4

0.32

MVP

0.17

MPC

0.45

ClinPred

0.10

GERP RS

0.19

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.29

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over