Genetic Variant DAPL1:p.Leu60Pro (chr2-158807087-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001017920.3(DAPL1):c.179T>C(p.Leu60Pro) variant causes a missense change. The variant allele was found at a frequency of 0.46 in 1,610,226 control chromosomes in the GnomAD database, including 177,071 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.49 ( 18774 hom., cov: 31)

Exomes 𝑓: 0.46 ( 158297 hom. )

Consequence

DAPL1
NM_001017920.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.14

Variant links:

Genes affected

DAPL1 (HGNC:21490): (death associated protein like 1) Predicted to enable death domain binding activity. Predicted to be involved in apoptotic signaling pathway; cellular response to amino acid starvation; and negative regulation of autophagy. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DAPL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.931708E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAPL1	NM_001017920.3 link	c.179T>C	p.Leu60Pro	missense_variant	Exon 3 of 4	ENST00000309950.8	NP_001017920.2	A0PJW8M1E9T5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DAPL1	ENST00000309950.8 link	c.179T>C	p.Leu60Pro	missense_variant	Exon 3 of 4	1	NM_001017920.3	ENSP00000309538.4	A0PJW8
DAPL1	ENST00000621326.4 link	c.179T>C	p.Leu60Pro	missense_variant	Exon 3 of 5	1		ENSP00000479872.1	M1EA23
DAPL1	ENST00000343761.4 link	c.104T>C	p.Leu35Pro	missense_variant	Exon 2 of 4	3		ENSP00000385306.2	H0Y3U5
DAPL1	ENST00000409042.5 link	c.179T>C	p.Leu60Pro	missense_variant	Exon 3 of 5	4		ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

74232

AN:

151902

Hom.:

18747

Cov.:

show subpopulations

Gnomad AFR

AF:

0.545

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.799

Gnomad SAS

AF:

0.583

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.447

GnomAD3 exomes

AF:

0.514

AC:

128436

AN:

250090

Hom.:

35152

AF XY:

0.506

AC XY:

68436

AN XY:

135202

show subpopulations

Gnomad AFR exome

AF:

0.556

Gnomad AMR exome

AF:

0.694

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.795

Gnomad SAS exome

AF:

0.575

Gnomad FIN exome

AF:

0.390

Gnomad NFE exome

AF:

0.426

Gnomad OTH exome

AF:

0.481

GnomAD4 exome

AF:

0.457

AC:

666751

AN:

1458206

Hom.:

158297

Cov.:

AF XY:

0.459

AC XY:

332638

AN XY:

725470

show subpopulations

Gnomad4 AFR exome

AF:

0.552

Gnomad4 AMR exome

AF:

0.681

Gnomad4 ASJ exome

AF:

0.408

Gnomad4 EAS exome

AF:

0.800

Gnomad4 SAS exome

AF:

0.575

Gnomad4 FIN exome

AF:

0.399

Gnomad4 NFE exome

AF:

0.427

Gnomad4 OTH exome

AF:

0.473

GnomAD4 genome

AF:

0.489

AC:

74304

AN:

152020

Hom.:

18774

Cov.:

AF XY:

0.494

AC XY:

36683

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.545

Gnomad4 AMR

AF:

0.584

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.800

Gnomad4 SAS

AF:

0.583

Gnomad4 FIN

AF:

0.400

Gnomad4 NFE

AF:

0.423

Gnomad4 OTH

AF:

0.447

Alfa

AF:

0.446

Hom.:

38566

Bravo

AF:

0.507

TwinsUK

AF:

0.420

AC:

1558

ALSPAC

AF:

0.430

AC:

1656

ESP6500AA

AF:

0.549

AC:

2420

ESP6500EA

AF:

0.434

AC:

3735

ExAC

AF:

0.507

AC:

61515

Asia WGS

AF:

0.630

AC:

2191

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0060

T;.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.67

T;T;T

MetaRNN

Benign

0.0000029

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;.;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.6

N;.;D

REVEL

Benign

0.068

Sift

Benign

0.045

D;.;D

Sift4G

Benign

0.16

T;D;D

Polyphen

0.76

P;.;.

Vest4

0.44

MPC

0.052

ClinPred

0.041

GERP RS

5.6

Varity_R

0.80

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over