Variant 12-95141380-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018351.4(FGD6):c.2837+8T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,613,174 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 72 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 63 hom. )

Consequence

FGD6
NM_018351.4 splice_region, intron

Scores

Splicing: ADA: 0.00004508

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.117

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-95141380-A-C is Benign according to our data. Variant chr12-95141380-A-C is described in ClinVar as [Benign]. Clinvar id is 781089.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD6	NM_018351.4 linkuse as main transcript	c.2837+8T>G		splice_region_variant, intron_variant		ENST00000343958.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
FGD6	ENST00000343958.9 linkuse as main transcript	c.2837+8T>G	splice_region_variant, intron_variant	1	NM_018351.4	P1	Q6ZV73-1
FGD6	ENST00000549499.1 linkuse as main transcript	c.2837+8T>G	splice_region_variant, intron_variant	1
FGD6	ENST00000451107.3 linkuse as main transcript	c.*232+8T>G	splice_region_variant, intron_variant, NMD_transcript_variant	1
FGD6	ENST00000546711.5 linkuse as main transcript	c.2837+8T>G	splice_region_variant, intron_variant	5			Q6ZV73-2

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

2409

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0550

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00629

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00413

AC:

1037

AN:

250840

Hom.:

AF XY:

0.00305

AC XY:

413

AN XY:

135518

show subpopulations

Gnomad AFR exome

AF:

0.0571

Gnomad AMR exome

AF:

0.00258

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:

0.0000793

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00163

AC:

2375

AN:

1460888

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

1037

AN XY:

726666

show subpopulations

Gnomad4 AFR exome

AF:

0.0603

Gnomad4 AMR exome

AF:

0.00307

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00318

GnomAD4 genome

AF:

0.0159

AC:

2427

AN:

152286

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1114

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0553

Gnomad4 AMR

AF:

0.00628

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00769

Hom.:

Bravo

AF:

0.0177

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.6

DANN

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000045

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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