Variant 4-99816956-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014395.3(DAPP1):c.43G>A(p.Asp15Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,609,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

DAPP1
NM_014395.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

Variant links:

Genes affected

DAPP1 (HGNC:16500): (dual adaptor of phosphotyrosine and 3-phosphoinositides 1) Enables phosphatidylinositol-3,4,5-trisphosphate binding activity and phosphatidylinositol-3,4-bisphosphate binding activity. Predicted to be involved in signal transduction. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

DAPP1 links:

DAPP1 (HGNC:):

DAPP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07648522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAPP1	NM_014395.3 linkuse as main transcript	c.43G>A	p.Asp15Asn	missense_variant	1/9	ENST00000512369.2	NP_055210.2	Q9UN19-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DAPP1	ENST00000512369.2 linkuse as main transcript	c.43G>A	p.Asp15Asn	missense_variant	1/9	1	NM_014395.3	ENSP00000423602.1	Q9UN19-1
DAPP1	ENST00000296414.11 linkuse as main transcript	c.43G>A	p.Asp15Asn	missense_variant	1/10	1		ENSP00000296414.7	J3KNB3
DAPP1	ENST00000507994.1 linkuse as main transcript	n.107G>A		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000478

GnomAD3 exomes

AF:

0.00000834

AC:

AN:

239906

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

129826

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000920

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1456778

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

724042

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000991

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 12, 2024

The c.43G>A (p.D15N) alteration is located in exon 1 (coding exon 1) of the DAPP1 gene. This alteration results from a G to A substitution at nucleotide position 43, causing the aspartic acid (D) at amino acid position 15 to be replaced by an asparagine (N). 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

0.078

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

.;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.81

.;L

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.94

N;N

REVEL

Benign

0.095

Sift

Benign

0.055

T;T

Sift4G

Uncertain

0.046

D;D

Polyphen

0.0

.;B

Vest4

0.13

MVP

0.78

MPC

0.57

ClinPred

0.13

GERP RS

4.0

Varity_R

0.051

gMVP

0.29

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over