Variant 12-95172699-G-T 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_018351.4(FGD6):c.2487C>A(p.Asp829Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,460,540 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: 0.000015 ( 0 hom. )

Consequence

FGD6
NM_018351.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.843

Variant links:

Genes affected

FGD6 (HGNC:21740): (FYVE, RhoGEF and PH domain containing 6) 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. Predicted to be located in Golgi apparatus; lamellipodium; and ruffle. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FGD6 links:

Genome browser will be placed here

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=0.14945108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGD6	NM_018351.4 linkuse as main transcript	c.2487C>A	p.Asp829Glu	missense_variant	3/21	ENST00000343958.9	NP_060821.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGD6	ENST00000343958.9 linkuse as main transcript	c.2487C>A	p.Asp829Glu	missense_variant	3/21	1	NM_018351.4	ENSP00000344446	P1	Q6ZV73-1
FGD6	ENST00000549499.1 linkuse as main transcript	c.2487C>A	p.Asp829Glu	missense_variant	3/16	1		ENSP00000449005
FGD6	ENST00000451107.3 linkuse as main transcript	c.62C>A	p.Thr21Asn	missense_variant, NMD_transcript_variant	2/20	1		ENSP00000408291
FGD6	ENST00000546711.5 linkuse as main transcript	c.2487C>A	p.Asp829Glu	missense_variant	3/19	5		ENSP00000450342		Q6ZV73-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250638

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135420

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:

0.0000463

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1460540

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726428

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:

0.0000187

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000548

EpiControl

AF:

0.00

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

Oct 05, 2023

The c.2487C>A (p.D829E) alteration is located in exon 3 (coding exon 3) of the FGD6 gene. This alteration results from a C to A substitution at nucleotide position 2487, causing the aspartic acid (D) at amino acid position 829 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

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.016

T;.;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.040

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.0093

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.5

M;M;.

MutationTaster

Benign

0.77

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.047

Sift

Benign

0.084

T;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.041

B;.;.

Vest4

0.082

MutPred

0.24

Gain of solvent accessibility (P = 0.3089);Gain of solvent accessibility (P = 0.3089);Gain of solvent accessibility (P = 0.3089);

MVP

0.59

MPC

0.12

ClinPred

0.20

GERP RS

4.0

Varity_R

0.066

gMVP

0.067

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