Variant chr4-99863812-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014395.3(DAPP1):c.643G>A(p.Ala215Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,544 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DAPP1
NM_014395.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.27

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAPP1	NM_014395.3 linkuse as main transcript	c.643G>A	p.Ala215Thr	missense_variant	7/9	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.643G>A	p.Ala215Thr	missense_variant	7/9	1	NM_014395.3	ENSP00000423602.1	Q9UN19-1
DAPP1	ENST00000296414.11 linkuse as main transcript	c.643G>A	p.Ala215Thr	missense_variant	7/10	1		ENSP00000296414.7	J3KNB3
DAPP1	ENST00000507994.1 linkuse as main transcript	n.576G>A		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450544

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720820

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 13, 2023

The c.643G>A (p.A215T) alteration is located in exon 7 (coding exon 7) of the DAPP1 gene. This alteration results from a G to A substitution at nucleotide position 643, causing the alanine (A) at amino acid position 215 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

Uncertain

0.50

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

.;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.77

N;N

REVEL

Benign

0.13

Sift

Benign

0.10

T;T

Sift4G

Uncertain

0.037

D;D

Polyphen

0.94

.;P

Vest4

0.60

MutPred

0.50

Gain of catalytic residue at F218 (P = 0.0998);Gain of catalytic residue at F218 (P = 0.0998);

MVP

0.74

MPC

1.4

ClinPred

0.85

GERP RS

5.7

Varity_R

0.29

gMVP

0.55

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over