Genetic Variant DAP:p.Pro4Thr (chr5-10761059-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004394.3(DAP):c.10C>A(p.Pro4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 150,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DAP
NM_004394.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

Publications

0 publications found

Variant links:

Genes affected

DAP (HGNC:2672): (death associated protein) This gene encodes a basic, proline-rich, 15-kD protein. The protein acts as a positive mediator of programmed cell death that is induced by interferon-gamma. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

DAP links:

DAP-DT (HGNC:55214): (DAP divergent transcript)

DAP-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26759443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAP	NM_004394.3 link	c.10C>A	p.Pro4Thr	missense_variant	Exon 1 of 4	ENST00000230895.11	NP_004385.1	P51397
DAP	NM_001291963.2 link	c.10C>A	p.Pro4Thr	missense_variant	Exon 1 of 3		NP_001278892.1	P51397B4DQ75
DAP-DT	NR_187555.1 link	n.24G>T		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAP	ENST00000230895.11 link	c.10C>A	p.Pro4Thr	missense_variant	Exon 1 of 4	1	NM_004394.3	ENSP00000230895.7		P51397

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

150272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000970

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1074050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

511832

African (AFR)

AF:

0.00

AC:

AN:

22232

American (AMR)

AF:

0.00

AC:

AN:

9568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11920

East Asian (EAS)

AF:

0.00

AC:

AN:

24706

South Asian (SAS)

AF:

0.00

AC:

AN:

22646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35038

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2722

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

904572

Other (OTH)

AF:

0.00

AC:

AN:

40646

GnomAD4 genome

AF:

0.0000266

AC:

AN:

150272

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

73306

show subpopulations

African (AFR)

AF:

0.0000970

AC:

AN:

41250

American (AMR)

AF:

0.00

AC:

AN:

15132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67252

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 10, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.10C>A (p.P4T) alteration is located in exon 1 (coding exon 1) of the DAP gene. This alteration results from a C to A substitution at nucleotide position 10, causing the proline (P) at amino acid position 4 to be replaced by a threonine (T). 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

0.19

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.

PhyloP100

2.4

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.16

Sift

Benign

0.22

T;D

Sift4G

Benign

0.48

T;T

Polyphen

1.0

D;D

Vest4

0.31

MVP

0.69

MPC

0.77

ClinPred

0.71

GERP RS

2.9

PromoterAI

-0.042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.080

gMVP

0.010

Mutation Taster

=98/2

polymorphism

(source)

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

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5-10761059-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over