dbSNP rs1409337925: DAP:p.Pro72Leu (chr5-10681150-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_004394.3(DAP):c.215C>T(p.Pro72Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,516,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

DAP
NM_004394.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.37

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.777

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAP	NM_004394.3 link	c.215C>T	p.Pro72Leu	missense_variant	Exon 4 of 4	ENST00000230895.11	NP_004385.1	P51397
DAP	NM_001291963.2 link	c.172C>T	p.Arg58Trp	missense_variant	Exon 3 of 3		NP_001278892.1	P51397B4DQ75

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DAP	ENST00000230895.11 link	c.215C>T	p.Pro72Leu	missense_variant	Exon 4 of 4	1	NM_004394.3	ENSP00000230895.7	P51397
DAP	ENST00000432074.2 link	c.172C>T	p.Arg58Trp	missense_variant	Exon 3 of 3	2		ENSP00000394163.2	B4DQ75
DAP	ENST00000514882.5 link	n.503C>T		non_coding_transcript_exon_variant	Exon 4 of 4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000673

AC:

AN:

148642

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000144

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000147

AC:

AN:

1363914

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

668308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30532

American (AMR)

AF:

0.00

AC:

AN:

28540

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20650

East Asian (EAS)

AF:

0.00

AC:

AN:

38316

South Asian (SAS)

AF:

0.00

AC:

AN:

69248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5320

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

1066278

Other (OTH)

AF:

0.00

AC:

AN:

56086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

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:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2112

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 06, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.215C>T (p.P72L) alteration is located in exon 4 (coding exon 4) of the DAP gene. This alteration results from a C to T substitution at nucleotide position 215, causing the proline (P) at amino acid position 72 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

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.026

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.58

MutationAssessor

Pathogenic

3.1

PhyloP100

7.4

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-6.8

REVEL

Uncertain

0.32

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.036

Polyphen

1.0

Vest4

0.55

MVP

0.71

MPC

0.29

ClinPred

0.86

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

Mutation Taster

=89/11

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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rs1409337925

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