dbSNP rs1368321606: AGAP4:p.Ala627Val (chr10-45826096-G-A) – 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.1880C>T(p.Ala627Val) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000018 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

AGAP4
NM_001276343.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87

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=0.2904449).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP4	NM_001276343.3 link	c.1880C>T	p.Ala627Val	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.1880C>T	p.Ala627Val	missense_variant	Exon 8 of 8	1	NM_001276343.3	ENSP00000483751.2		A0A087X0Z1
AGAP4	ENST00000448048.7 link	c.1811C>T	p.Ala604Val	missense_variant	Exon 7 of 7	1		ENSP00000392513.2		Q96P64

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

128554

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000235

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000171

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000179

AC:

AN:

1282732

Hom.:

Cov.:

AF XY:

0.00000938

AC XY:

AN XY:

639348

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000793

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000186

Gnomad4 OTH exome

AF:

0.0000369

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000156

AC:

AN:

128554

Hom.:

Cov.:

AF XY:

0.0000326

AC XY:

AN XY:

61290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000235

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000171

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1811C>T (p.A604V) alteration is located in exon 7 (coding exon 7) of the AGAP4 gene. This alteration results from a C to T substitution at nucleotide position 1811, causing the alanine (A) at amino acid position 604 to be replaced by a valine (V). 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

0.18

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.044

T;.;.;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.0031

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.0

M;.;.;.

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.1

D;.;.;.

REVEL

Benign

0.19

Sift

Benign

0.22

T;.;.;.

Sift4G

Benign

0.080

T;T;T;T

Polyphen

0.97

D;.;.;.

Vest4

0.49

MVP

0.085

ClinPred

0.65

Varity_R

0.21

gMVP

0.084

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