chr4-99840374-G-A

Position:

• chr4-99840374-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014395.3(DAPP1):​c.310G>A​(p.Asp104Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DAPP1 NM_014395.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.88

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38753778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAPP1	NM_014395.3	c.310G>A	p.Asp104Asn	missense_variant	3/9	ENST00000512369.2	NP_055210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAPP1	ENST00000512369.2	c.310G>A	p.Asp104Asn	missense_variant	3/9	1	NM_014395.3	ENSP00000423602.1
DAPP1	ENST00000296414.11	c.310G>A	p.Asp104Asn	missense_variant	3/10	1		ENSP00000296414.7
DAPP1	ENST00000507994.1	n.374G>A		non_coding_transcript_exon_variant	3/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458902 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725712

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

DAPP1-related condition Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 23, 2024

The DAPP1 c.310G>A variant is predicted to result in the amino acid substitution p.Asp104Asn. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.79	.;D
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Uncertain	0.41	D
MutationAssessor	Benign	2.0	.;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.52
Sift	Uncertain	0.022	D;D
Sift4G	Benign	0.24	T;T
Polyphen		0.35	.;B
Vest4		0.35
MutPred		0.57		Loss of ubiquitination at K103 (P = 0.065);Loss of ubiquitination at K103 (P = 0.065);
MVP		0.93
MPC		1.1
ClinPred		0.94	D
GERP RS		5.5
Varity_R		0.16
gMVP		0.59

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.

Other links and lift over

hg19: chr4-100761531;