Variant chrX-54446073-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004463.3(FGD1):c.*36C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0973 in 1,118,043 control chromosomes in the GnomAD database, including 6,565 homozygotes. There are 33,846 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 597 hom., 2966 hem., cov: 22)

Exomes 𝑓: 0.099 ( 5968 hom. 30880 hem. )

Consequence

FGD1
NM_004463.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.295

Variant links:

Genes affected

FGD1 (HGNC:3663): (FYVE, RhoGEF and PH domain containing 1) This gene encodes a protein that contains Dbl (DH) and pleckstrin (PH) homology domains and is similar to the Rho family of small GTP-binding proteins. The encoded protein specifically binds to the Rho family GTPase Cdc42Hs and can stimulate the GDP-GTP exchange of the isoprenylated form of Cdc42Hs. It also stimulates the mitogen activated protein kinase cascade leading to c-Jun kinase SAPK/JNK1 activation. Defects in this gene are the cause of the faciogenital dysplasia in Aarskog-Scott syndrome and a syndromatic form of X-linked cognitive disability. [provided by RefSeq, Jul 2017]

FGD1 links:

TSR2 (HGNC:25455): (TSR2 ribosome maturation factor) The protein encoded by this gene appears to repress the transcription of NF-kappaB and may be involved in apoptosis. Defects in this gene are a cause of Diamond-Blackfan anemia. [provided by RefSeq, Oct 2016]

TSR2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant X-54446073-G-A is Benign according to our data. Variant chrX-54446073-G-A is described in ClinVar as [Benign]. Clinvar id is 95076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD1	NM_004463.3 linkuse as main transcript	c.*36C>T		3_prime_UTR_variant	18/18	ENST00000375135.4
TSR2	NM_058163.3 linkuse as main transcript	c.*1523G>A		3_prime_UTR_variant	5/5	ENST00000375151.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD1	ENST00000375135.4 linkuse as main transcript	c.*36C>T		3_prime_UTR_variant	18/18	1	NM_004463.3	P1
TSR2	ENST00000375151.5 linkuse as main transcript	c.*1523G>A		3_prime_UTR_variant	5/5	1	NM_058163.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0866

AC:

9621

AN:

111141

Hom.:

600

Cov.:

AF XY:

0.0890

AC XY:

2967

AN XY:

33329

show subpopulations

Gnomad AFR

AF:

0.0158

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.0894

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.0855

Gnomad MID

AF:

0.0462

Gnomad NFE

AF:

0.0742

Gnomad OTH

AF:

0.0990

GnomAD3 exomes

AF:

0.142

AC:

21203

AN:

149170

Hom.:

2085

AF XY:

0.130

AC XY:

5736

AN XY:

44280

show subpopulations

Gnomad AFR exome

AF:

0.0129

Gnomad AMR exome

AF:

0.286

Gnomad ASJ exome

AF:

0.0897

Gnomad EAS exome

AF:

0.478

Gnomad SAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.0907

Gnomad NFE exome

AF:

0.0748

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.0985

AC:

99176

AN:

1006852

Hom.:

5968

Cov.:

AF XY:

0.102

AC XY:

30880

AN XY:

303936

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.284

Gnomad4 ASJ exome

AF:

0.0898

Gnomad4 EAS exome

AF:

0.509

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.0909

Gnomad4 NFE exome

AF:

0.0754

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.0864

AC:

9607

AN:

111191

Hom.:

597

Cov.:

AF XY:

0.0888

AC XY:

2966

AN XY:

33387

show subpopulations

Gnomad4 AFR

AF:

0.0157

Gnomad4 AMR

AF:

0.219

Gnomad4 ASJ

AF:

0.0894

Gnomad4 EAS

AF:

0.471

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.0855

Gnomad4 NFE

AF:

0.0742

Gnomad4 OTH

AF:

0.0977

Alfa

AF:

0.0875

Hom.:

4409

Bravo

AF:

0.100

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Mar 07, 2013

- -

Aarskog syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.0

DANN

Benign

0.84

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