Variant chr10-73674791-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000374094.9(AGAP5):c.1869C>G(p.Asp623Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AGAP5
ENST00000374094.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.448

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25445563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AGAP5	NM_001144000.4 linkuse as main transcript	c.1869C>G	p.Asp623Glu	missense_variant	8/8	ENST00000374094.9	NP_001137472.1
BMS1P4-AGAP5	NR_160426.1 linkuse as main transcript	n.4136C>G		non_coding_transcript_exon_variant	20/20
BMS1P4-AGAP5	NR_160425.1 linkuse as main transcript	n.3348C>G		non_coding_transcript_exon_variant	19/19
BMS1P4-AGAP5	NR_160427.1 linkuse as main transcript	n.3280C>G		non_coding_transcript_exon_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGAP5	ENST00000374094.9 linkuse as main transcript	c.1869C>G	p.Asp623Glu	missense_variant	8/8	1	NM_001144000.4	ENSP00000363207	A2
SYNPO2L-AS1	ENST00000668336.1 linkuse as main transcript	n.546G>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151764

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000438

AC:

AN:

228148

Hom.:

AF XY:

0.00000793

AC XY:

AN XY:

126154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000954

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000123

AC:

AN:

1459622

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000659

AC:

AN:

151764

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74132

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000257

AC:

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

Aug 08, 2022

The c.1869C>G (p.D623E) 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 1869, causing the aspartic acid (D) at amino acid position 623 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

Benign

0.26

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.028

.;.;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.0048

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.4

.;.;L

MutationTaster

Benign

0.75

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.6

.;D;D

REVEL

Benign

0.11

Sift

Benign

0.073

.;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

1.0

.;.;D

Vest4

0.21

MutPred

0.43

Gain of disorder (P = 0.0709);.;Gain of disorder (P = 0.0709);

MVP

0.030

ClinPred

0.41

Varity_R

0.15

gMVP

0.064

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