Variant 12-95152845-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_018351.4(FGD6):c.2655-4A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,613,428 control chromosomes in the GnomAD database, including 22 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 0.0061 ( 16 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 6 hom. )

Consequence

FGD6
NM_018351.4 splice_region, intron

Scores

Splicing: ADA: 0.0006705

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.950

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 12-95152845-T-A is Benign according to our data. Variant chr12-95152845-T-A is described in ClinVar as [Benign]. Clinvar id is 784253.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00607 (924/152162) while in subpopulation AFR AF= 0.0211 (875/41516). AF 95% confidence interval is 0.0199. There are 16 homozygotes in gnomad4. There are 433 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGD6	NM_018351.4 linkuse as main transcript	c.2655-4A>T		splice_region_variant, intron_variant		ENST00000343958.9	NP_060821.3	Q6ZV73-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
FGD6	ENST00000343958.9 linkuse as main transcript	c.2655-4A>T	splice_region_variant, intron_variant	1	NM_018351.4	ENSP00000344446.4	Q6ZV73-1
FGD6	ENST00000549499.1 linkuse as main transcript	c.2655-4A>T	splice_region_variant, intron_variant	1		ENSP00000449005.1	F8VY01
FGD6	ENST00000451107.3 linkuse as main transcript	n.*50-4A>T	splice_region_variant, intron_variant	1		ENSP00000408291.3	F8VWT6
FGD6	ENST00000546711.5 linkuse as main transcript	c.2655-4A>T	splice_region_variant, intron_variant	5		ENSP00000450342.1	Q6ZV73-2

Frequencies

GnomAD3 genomes

AF:

0.00600

AC:

912

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

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:

0.00623

GnomAD3 exomes

AF:

0.00161

AC:

402

AN:

250212

Hom.:

AF XY:

0.00118

AC XY:

159

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.0228

Gnomad AMR exome

AF:

0.000725

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:

0.0000265

Gnomad OTH exome

AF:

0.000985

GnomAD4 exome

AF:

0.000602

AC:

880

AN:

1461266

Hom.:

Cov.:

AF XY:

0.000534

AC XY:

388

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.0228

Gnomad4 AMR exome

AF:

0.000917

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00607

AC:

924

AN:

152162

Hom.:

Cov.:

AF XY:

0.00582

AC XY:

433

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0211

Gnomad4 AMR

AF:

0.00236

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:

0.00617

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.00698

Asia WGS

AF:

0.00173

AC:

AN:

3476

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

Labcorp Genetics (formerly Invitae), Labcorp

Apr 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00067

dbscSNV1_RF

Benign

0.032

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