Variant 3-14819702-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152536.4(FGD5):c.631G>A(p.Gly211Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,537,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

FGD5
NM_152536.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.76

Variant links:

Genes affected

FGD5 (HGNC:19117): (FYVE, RhoGEF and PH domain containing 5) Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in several processes, including filopodium assembly; regulation of GTPase activity; and regulation of cell shape. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FGD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04952097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGD5	NM_152536.4 linkuse as main transcript	c.631G>A	p.Gly211Arg	missense_variant	1/20	ENST00000285046.10	NP_689749.3	Q6ZNL6-1A0A2X0SFF2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FGD5	ENST00000285046.10 linkuse as main transcript	c.631G>A	p.Gly211Arg	missense_variant	1/20	1	NM_152536.4	ENSP00000285046.5	Q6ZNL6-1
FGD5	ENST00000543601 linkuse as main transcript	c.-93G>A		5_prime_UTR_variant	1/19	1		ENSP00000445949.1	B7ZM68
FGD5	ENST00000640506.1 linkuse as main transcript	c.760G>A	p.Gly254Arg	missense_variant	2/2	5		ENSP00000492654.1	A0A1W2PRG7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152106

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

141936

Hom.:

AF XY:

0.0000404

AC XY:

AN XY:

74308

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:

0.000154

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000166

AC:

AN:

1384974

Hom.:

Cov.:

AF XY:

0.0000191

AC XY:

AN XY:

681184

show subpopulations

Gnomad4 AFR exome

AF:

0.0000638

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000196

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000467

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000221

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

Jul 14, 2024

The c.631G>A (p.G211R) alteration is located in exon 1 (coding exon 1) of the FGD5 gene. This alteration results from a G to A substitution at nucleotide position 631, causing the glycine (G) at amino acid position 211 to be replaced by an arginine (R). 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

0.075

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.0050

DANN

Benign

0.59

DEOGEN2

Benign

0.0025

.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.76

.;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.27

Sift

Benign

0.22

.;T

Sift4G

Benign

0.32

.;T

Polyphen

0.0020

.;B

Vest4

0.048

MutPred

0.10

.;Gain of helix (P = 0.027);

MVP

0.31

MPC

0.19

ClinPred

0.036

GERP RS

-11

Varity_R

0.065

gMVP

0.038

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