Variant 10-73675137-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000374094.9(AGAP5):c.1523G>C(p.Ser508Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,610,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AGAP5
ENST00000374094.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39641914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AGAP5	NM_001144000.4 linkuse as main transcript	c.1523G>C	p.Ser508Thr	missense_variant	8/8	ENST00000374094.9	NP_001137472.1
BMS1P4-AGAP5	NR_160426.1 linkuse as main transcript	n.3790G>C		non_coding_transcript_exon_variant	20/20
BMS1P4-AGAP5	NR_160425.1 linkuse as main transcript	n.3002G>C		non_coding_transcript_exon_variant	19/19
BMS1P4-AGAP5	NR_160427.1 linkuse as main transcript	n.2934G>C		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.1523G>C	p.Ser508Thr	missense_variant	8/8	1	NM_001144000.4	ENSP00000363207	A2
SYNPO2L-AS1	ENST00000668336.1 linkuse as main transcript	n.892C>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149576

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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:

0.0000139

AC:

AN:

72102

Hom.:

AF XY:

0.00

AC XY:

AN XY:

35502

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000115

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:

0.00000137

AC:

AN:

1460648

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726576

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

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

AF:

0.00000669

AC:

AN:

149576

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72920

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Feb 07, 2023

The c.1523G>C (p.S508T) alteration is located in exon 8 (coding exon 8) of the AGAP5 gene. This alteration results from a G to C substitution at nucleotide position 1523, causing the serine (S) at amino acid position 508 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.13

.;.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.0055

MetaRNN

Benign

0.40

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.9

.;.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.2

.;N;N

REVEL

Benign

0.23

Sift

Uncertain

0.0030

.;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.96

.;.;D

Vest4

0.20

MutPred

0.55

Loss of disorder (P = 0.0736);.;Loss of disorder (P = 0.0736);

MVP

0.030

ClinPred

0.27

Varity_R

0.32

gMVP

0.031

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