Variant 10-73675135-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001144000.4(AGAP5):c.1525C>G(p.Leu509Val) variant causes a missense change. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00082 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AGAP5
NM_001144000.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20

Variant links:

Genes affected

AGAP5 (HGNC:23467): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 5) 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]

AGAP5 links:

SYNPO2L-AS1 (HGNC:55242): (SYNPO2L antisense RNA 1)

SYNPO2L-AS1 links:

BMS1P4-AGAP5 (HGNC:):

BMS1P4-AGAP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AGAP5	NM_001144000.4 linkuse as main transcript	c.1525C>G	p.Leu509Val	missense_variant	8/8	ENST00000374094.9
BMS1P4-AGAP5	NR_160426.1 linkuse as main transcript	n.3792C>G		non_coding_transcript_exon_variant	20/20
BMS1P4-AGAP5	NR_160425.1 linkuse as main transcript	n.3004C>G		non_coding_transcript_exon_variant	19/19
BMS1P4-AGAP5	NR_160427.1 linkuse as main transcript	n.2936C>G		non_coding_transcript_exon_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGAP5	ENST00000374094.9 linkuse as main transcript	c.1525C>G	p.Leu509Val	missense_variant	8/8	1	NM_001144000.4	A2
SYNPO2L-AS1	ENST00000668336.1 linkuse as main transcript	n.890G>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149640

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000134

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000700

Gnomad OTH

AF:

0.000506

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000819

AC:

1196

AN:

1460642

Hom.:

Cov.:

AF XY:

0.000812

AC XY:

590

AN XY:

726576

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000994

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000401

AC:

AN:

149758

Hom.:

Cov.:

AF XY:

0.000369

AC XY:

AN XY:

73084

show subpopulations

Gnomad4 AFR

AF:

0.000245

Gnomad4 AMR

AF:

0.000134

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000700

Gnomad4 OTH

AF:

0.000501

Alfa

AF:

0.0000641

Hom.:

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

Apr 24, 2024

The c.1525C>G (p.L509V) alteration is located in exon 8 (coding exon 8) of the AGAP5 gene. This alteration results from a C to G substitution at nucleotide position 1525, causing the leucine (L) at amino acid position 509 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

0.13

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.66

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.0084

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-0.62

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.48

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.58

.;.;P

Vest4

0.47

MutPred

0.81

Gain of MoRF binding (P = 0.0904);.;Gain of MoRF binding (P = 0.0904);

MVP

0.085

ClinPred

0.48

Varity_R

0.43

gMVP

0.037

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