Variant rs10507047 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018351.4(FGD6):c.770A>G(p.Gln257Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,613,868 control chromosomes in the GnomAD database, including 10,259 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 989 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9270 hom. )

Consequence

FGD6
NM_018351.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.63

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033772886).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGD6	NM_018351.4 linkuse as main transcript	c.770A>G	p.Gln257Arg	missense_variant	2/21	ENST00000343958.9	NP_060821.3	Q6ZV73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FGD6	ENST00000343958.9 linkuse as main transcript	c.770A>G	p.Gln257Arg	missense_variant	2/21	1	NM_018351.4	ENSP00000344446.4	Q6ZV73-1
FGD6	ENST00000549499.1 linkuse as main transcript	c.770A>G	p.Gln257Arg	missense_variant	2/16	1		ENSP00000449005.1	F8VY01
FGD6	ENST00000451107.3 linkuse as main transcript	n.16+6711A>G		intron_variant		1		ENSP00000408291.3	F8VWT6
FGD6	ENST00000546711.5 linkuse as main transcript	c.770A>G	p.Gln257Arg	missense_variant	2/19	5		ENSP00000450342.1	Q6ZV73-2

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16614

AN:

152138

Hom.:

982

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0982

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.0844

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.0912

Gnomad MID

AF:

0.0892

Gnomad NFE

AF:

0.0990

Gnomad OTH

AF:

0.126

GnomAD3 exomes

AF:

0.120

AC:

30208

AN:

250828

Hom.:

2151

AF XY:

0.116

AC XY:

15775

AN XY:

135574

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.0808

Gnomad EAS exome

AF:

0.225

Gnomad SAS exome

AF:

0.0977

Gnomad FIN exome

AF:

0.0918

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.106

AC:

154750

AN:

1461612

Hom.:

9270

Cov.:

AF XY:

0.106

AC XY:

76722

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.0955

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.0771

Gnomad4 EAS exome

AF:

0.283

Gnomad4 SAS exome

AF:

0.0984

Gnomad4 FIN exome

AF:

0.0916

Gnomad4 NFE exome

AF:

0.0984

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.109

AC:

16643

AN:

152256

Hom.:

989

Cov.:

AF XY:

0.110

AC XY:

8159

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0983

Gnomad4 AMR

AF:

0.145

Gnomad4 ASJ

AF:

0.0844

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.0993

Gnomad4 FIN

AF:

0.0912

Gnomad4 NFE

AF:

0.0990

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.104

Hom.:

2343

Bravo

AF:

0.116

TwinsUK

AF:

0.0965

AC:

358

ALSPAC

AF:

0.0913

AC:

352

ESP6500AA

AF:

0.0958

AC:

422

ESP6500EA

AF:

0.0972

AC:

836

ExAC

AF:

0.117

AC:

14217

Asia WGS

AF:

0.215

AC:

745

AN:

3478

EpiCase

AF:

0.107

EpiControl

AF:

0.101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

8.2

DANN

Benign

0.97

DEOGEN2

Benign

0.019

T;.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.38

T;T;T

MetaRNN

Benign

0.0034

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.029

D;D;T

Sift4G

Benign

0.078

T;T;T

Polyphen

0.48

P;.;.

Vest4

0.042

MPC

0.13

ClinPred

0.014

GERP RS

4.8

Varity_R

0.090

gMVP

0.11

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over