dbSNP rs755003432: AGAP1:p.Asp55Glu (chr2-235709180-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001037131.3(AGAP1):c.165T>A(p.Asp55Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AGAP1
NM_001037131.3 missense, splice_region

Scores

Splicing: ADA: 0.0003867

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

AGAP1 (HGNC:16922): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 1) This gene encodes a member of an ADP-ribosylation factor GTPase-activating protein family involved in membrane trafficking and cytoskeleton dynamics. This gene functions as a direct regulator of the adaptor-related protein complex 3 on endosomes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

AGAP1 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 rank	MANE	Protein	UniProt
AGAP1	NM_001037131.3 link	c.165T>A	p.Asp55Glu	missense_variant, splice_region_variant	Exon 2 of 18	ENST00000304032.13	NP_001032208.1	Q9UPQ3-1B2RZG9
AGAP1	NM_014914.5 link	c.165T>A	p.Asp55Glu	missense_variant, splice_region_variant	Exon 2 of 17		NP_055729.2	Q9UPQ3-2
AGAP1	NM_001244888.2 link	c.165T>A	p.Asp55Glu	missense_variant, splice_region_variant	Exon 2 of 10		NP_001231817.1	Q9UPQ3-3B2RZG9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP1	ENST00000304032.13 link	c.165T>A	p.Asp55Glu	missense_variant, splice_region_variant	Exon 2 of 18	5	NM_001037131.3	ENSP00000307634.7		Q9UPQ3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251472

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

.;.;T;.;T;T;T;T

Eigen

Benign

0.058

Eigen_PC

Benign

-0.0026

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.88

D;D;D;T;T;D;D;D

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.37

T;T;T;D;T;D;D;D

MetaSVM

Uncertain

0.40

MutationAssessor

Benign

1.6

L;L;L;.;.;.;.;.

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-2.4

N;N;N;D;N;.;.;.

REVEL

Uncertain

0.40

Sift

Benign

0.24

T;T;T;T;T;.;.;.

Sift4G

Benign

0.18

T;T;T;T;T;T;T;T

Polyphen

1.0, 0.84

.;D;P;.;.;.;.;.

Vest4

0.70

MutPred

0.20

Loss of catalytic residue at D55 (P = 0.1278);Loss of catalytic residue at D55 (P = 0.1278);Loss of catalytic residue at D55 (P = 0.1278);.;.;.;.;.;

MVP

0.79

MPC

0.47

ClinPred

0.75

GERP RS

2.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.11

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00039

dbscSNV1_RF

Benign

0.024

SpliceAI score (max)

0.48

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.48

Position offset: 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