Variant chr12-95081528-T-C 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_018351.4(FGD6):c.4285A>G(p.Ile1429Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000374 in 1,605,374 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: 0.000041 ( 0 hom. )

Consequence

FGD6
NM_018351.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.311

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 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=0.030114084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGD6	NM_018351.4 linkuse as main transcript	c.4285A>G	p.Ile1429Val	missense_variant	21/21	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.4285A>G	p.Ile1429Val	missense_variant	21/21	1	NM_018351.4	ENSP00000344446.4	Q6ZV73-1
FGD6	ENST00000451107.3 linkuse as main transcript	n.*1680A>G		non_coding_transcript_exon_variant	20/20	1		ENSP00000408291.3	F8VWT6
FGD6	ENST00000451107.3 linkuse as main transcript	n.*1680A>G		3_prime_UTR_variant	20/20	1		ENSP00000408291.3	F8VWT6
FGD6	ENST00000548069.5 linkuse as main transcript	c.365A>G	p.Asn122Ser	missense_variant	4/4	3		ENSP00000448350.1	H0YI21

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

247764

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134130

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:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000406

AC:

AN:

1453250

Hom.:

Cov.:

AF XY:

0.0000332

AC XY:

AN XY:

722846

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:

0.0000523

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.82

DANN

Benign

0.62

DEOGEN2

Benign

0.030

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.57

M_CAP

Benign

0.0053

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.4

PrimateAI

Benign

0.36

PROVEAN

Benign

0.25

REVEL

Benign

0.064

Sift

Benign

0.95

Sift4G

Benign

0.92

Polyphen

0.0010

Vest4

0.066

MutPred

0.30

Gain of relative solvent accessibility (P = 0.1571);

MVP

0.23

MPC

0.096

ClinPred

0.025

GERP RS

-3.6

Varity_R

0.029

gMVP

0.095

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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