Variant 5-148394863-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_205836.3(FBXO38):c.87T>C(p.Tyr29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 1,599,796 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 15 hom. )

Consequence

FBXO38
NM_205836.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0830

Variant links:

Genes affected

FBXO38 (HGNC:28844): (F-box protein 38) This gene encodes a large protein that contains an F-box domain and may participate in protein ubiquitination. The encoded protein is a transcriptional co-activator of Krueppel-like factor 7 (Klf7). A heterozygous mutation in this gene was found in individuals with autosomal dominant distal hereditary motor neuronopathy type IID. There is a pseudogene for this gene on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

FBXO38 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

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

BP6

Variant 5-148394863-T-C is Benign according to our data. Variant chr5-148394863-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 473962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-148394863-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.083 with no splicing effect.

BS2

High AC in GnomAd4 at 382 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO38	NM_205836.3 linkuse as main transcript	c.87T>C	p.Tyr29=	synonymous_variant	2/22	ENST00000340253.10	NP_995308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO38	ENST00000340253.10 linkuse as main transcript	c.87T>C	p.Tyr29=	synonymous_variant	2/22	5	NM_205836.3	ENSP00000342023	P3	Q6PIJ6-1

Frequencies

GnomAD3 genomes

AF:

0.00251

AC:

382

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00463

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00285

AC:

681

AN:

238650

Hom.:

AF XY:

0.00275

AC XY:

356

AN XY:

129314

show subpopulations

Gnomad AFR exome

AF:

0.000453

Gnomad AMR exome

AF:

0.00348

Gnomad ASJ exome

AF:

0.000815

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00146

Gnomad FIN exome

AF:

0.00112

Gnomad NFE exome

AF:

0.00429

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00389

AC:

5626

AN:

1447508

Hom.:

Cov.:

AF XY:

0.00382

AC XY:

2748

AN XY:

719892

show subpopulations

Gnomad4 AFR exome

AF:

0.000735

Gnomad4 AMR exome

AF:

0.00310

Gnomad4 ASJ exome

AF:

0.000852

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00191

Gnomad4 FIN exome

AF:

0.00135

Gnomad4 NFE exome

AF:

0.00456

Gnomad4 OTH exome

AF:

0.00274

GnomAD4 genome

AF:

0.00251

AC:

382

AN:

152288

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00463

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00366

Hom.:

Bravo

AF:

0.00230

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	FBXO38: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2021	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

Distal hereditary motor neuropathy type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

FBXO38-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 22, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.1

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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