Variant 12-95172626-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018351.4(FGD6):c.2560G>A(p.Glu854Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FGD6
NM_018351.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2858432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD6	NM_018351.4 linkuse as main transcript	c.2560G>A	p.Glu854Lys	missense_variant	3/21	ENST00000343958.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD6	ENST00000343958.9 linkuse as main transcript	c.2560G>A	p.Glu854Lys	missense_variant	3/21	1	NM_018351.4	P1	Q6ZV73-1
FGD6	ENST00000549499.1 linkuse as main transcript	c.2560G>A	p.Glu854Lys	missense_variant	3/16	1
FGD6	ENST00000451107.3 linkuse as main transcript	c.135G>A	p.Glu45=	synonymous_variant, NMD_transcript_variant	2/20	1
FGD6	ENST00000546711.5 linkuse as main transcript	c.2560G>A	p.Glu854Lys	missense_variant	3/19	5			Q6ZV73-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250416

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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:

6.85e-7

AC:

AN:

1459152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725558

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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

Cov.:

ExAC

AF:

0.00000824

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

Jun 29, 2023

The c.2560G>A (p.E854K) alteration is located in exon 3 (coding exon 3) of the FGD6 gene. This alteration results from a G to A substitution at nucleotide position 2560, causing the glutamic acid (E) at amino acid position 854 to be replaced by a lysine (K). 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

0.16

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

T;.;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.5

M;M;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.86

P;.;.

Vest4

0.21

MutPred

0.25

Gain of ubiquitination at E854 (P = 0.0101);Gain of ubiquitination at E854 (P = 0.0101);Gain of ubiquitination at E854 (P = 0.0101);

MVP

0.55

MPC

0.37

ClinPred

0.73

GERP RS

5.9

Varity_R

0.17

gMVP

0.20

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