Variant chr3-14819311-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152536.4(FGD5):c.240C>A(p.Asp80Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,382,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

FGD5
NM_152536.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.11

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.074340284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD5	NM_152536.4 linkuse as main transcript	c.240C>A	p.Asp80Glu	missense_variant	1/20	ENST00000285046.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD5	ENST00000285046.10 linkuse as main transcript	c.240C>A	p.Asp80Glu	missense_variant	1/20	1	NM_152536.4	P1	Q6ZNL6-1
FGD5	ENST00000543601.5 linkuse as main transcript	c.-484C>A		5_prime_UTR_variant	1/19	1
FGD5	ENST00000640506.1 linkuse as main transcript	c.369C>A	p.Asp123Glu	missense_variant	2/2	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000213

AC:

AN:

140880

Hom.:

AF XY:

0.0000409

AC XY:

AN XY:

73394

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:

0.0000540

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000370

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1382076

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

AN XY:

679486

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000280

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000829

Hom.:

Bravo

AF:

0.00000756

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 12, 2023

The c.240C>A (p.D80E) alteration is located in exon 1 (coding exon 1) of the FGD5 gene. This alteration results from a C to A substitution at nucleotide position 240, causing the aspartic acid (D) at amino acid position 80 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

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.016

DANN

Benign

0.75

DEOGEN2

Benign

0.0039

.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.3

.;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.38

.;N

REVEL

Benign

0.19

Sift

Benign

0.035

.;D

Sift4G

Benign

0.66

.;T

Polyphen

0.053

.;B

Vest4

0.088

MutPred

0.14

.;Gain of glycosylation at P78 (P = 0.1004);

MVP

0.51

MPC

0.43

ClinPred

0.074

GERP RS

-11

Varity_R

0.048

gMVP

0.047

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