Genetic Variant NM_001276343.3:c.1844T>A (chr10-45826132-A-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001276343.3(AGAP4):c.1844T>A(p.Val615Glu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AGAP4
NM_001276343.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.42

Variant links:

Genes affected

AGAP4 (HGNC:23459): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 4) Predicted to enable GTPase activator activity and metal ion binding activity. Predicted to be involved in regulation of catalytic activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

AGAP4 links:

PARGP1-AGAP4 (HGNC:):

PARGP1-AGAP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3792787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP4	NM_001276343.3 link	c.1844T>A	p.Val615Glu	missense_variant	Exon 8 of 8	ENST00000616763.6	NP_001263272.2	Q96P64A0A087X0Z1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP4	ENST00000616763.6 link	c.1844T>A	p.Val615Glu	missense_variant	Exon 8 of 8	1	NM_001276343.3	ENSP00000483751.2		A0A087X0Z1
AGAP4	ENST00000448048.7 link	c.1775T>A	p.Val592Glu	missense_variant	Exon 7 of 7	1		ENSP00000392513.2		Q96P64

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

136048

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000146

Gnomad ASJ

AF:

0.000316

Gnomad EAS

AF:

0.000222

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00384

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000637

Gnomad OTH

AF:

0.00167

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00127

AC:

1798

AN:

1410378

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

881

AN XY:

701464

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.0000453

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000664

Gnomad4 FIN exome

AF:

0.00164

Gnomad4 NFE exome

AF:

0.00151

Gnomad4 OTH exome

AF:

0.000665

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000639

AC:

AN:

136142

Hom.:

Cov.:

AF XY:

0.000763

AC XY:

AN XY:

65538

show subpopulations

Gnomad4 AFR

AF:

0.000183

Gnomad4 AMR

AF:

0.000146

Gnomad4 ASJ

AF:

0.000316

Gnomad4 EAS

AF:

0.000223

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00384

Gnomad4 NFE

AF:

0.000637

Gnomad4 OTH

AF:

0.00165

Alfa

AF:

0.000337

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1775T>A (p.V592E) alteration is located in exon 7 (coding exon 7) of the AGAP4 gene. This alteration results from a T to A substitution at nucleotide position 1775, causing the valine (V) at amino acid position 592 to be replaced by a glutamic acid (E). 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

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.041

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.048

T;.;.;.

Eigen

Benign

-0.034

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.80

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Benign

0.0086

MetaRNN

Benign

0.38

T;T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Pathogenic

3.1

M;.;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-5.1

D;.;.;.

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

D;.;.;.

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.60

MVP

0.46

ClinPred

1.0

Varity_R

0.83

gMVP

0.16

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