8-144356205-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012162.4(FBXL6):c.1235A>G(p.Gln412Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000383 in 1,305,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000043 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

FBXL6
NM_012162.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

Publications

0 publications found

Variant links:

Genes affected

FBXL6 (HGNC:13603): (F-box and leucine rich repeat protein 6) This gene encodes a member of a family of proteins that are characterized by an F-box motif. The encoded protein also contains leucine-rich repeats. F-box-containing proteins comprise one of the subunits of the SCF (SKP1-cullin-F-box) complex, which functions in phosphorylation-dependent ubiquitination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

FBXL6 links:

SLC52A2 (HGNC:30224): (solute carrier family 52 member 2) This gene encodes a membrane protein which belongs to the riboflavin transporter family. In humans, riboflavin must be obtained by intestinal absorption because it cannot be synthesized by the body. The water-soluble vitamin riboflavin is processed to the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) which then act as intermediaries in many cellular metabolic reactions. Paralogous members of the riboflavin transporter gene family are located on chromosomes 17 and 20. Unlike other members of this family, this gene has higher expression in brain tissue than small intestine. Alternative splicing of this gene results in multiple transcript variants encoding the same protein. Mutations in this gene have been associated with Brown-Vialetto-Van Laere syndrome 2 - an autosomal recessive progressive neurologic disorder characterized by deafness, bulbar dysfunction, and axial and limb hypotonia. [provided by RefSeq, Jul 2012]

SLC52A2 Gene-Disease associations (from GenCC):

Brown-Vialetto-van Laere syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp

SLC52A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20995632).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012162.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL6	NM_012162.4	MANE Select	c.1235A>G	p.Gln412Arg	missense	Exon 8 of 9	NP_036294.2	Q8N531-1
	FBXL6	NM_024555.6		c.1217A>G	p.Gln406Arg	missense	Exon 8 of 9	NP_078831.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXL6	ENST00000331890.6	TSL:1 MANE Select	c.1235A>G	p.Gln412Arg	missense	Exon 8 of 9	ENSP00000330098.5	Q8N531-1
FBXL6	ENST00000455319.6	TSL:1	c.1217A>G	p.Gln406Arg	missense	Exon 8 of 9	ENSP00000403873.2	Q8N531-2
FBXL6	ENST00000530142.5	TSL:1	n.2623A>G		non_coding_transcript_exon	Exon 7 of 8

Frequencies

GnomAD3 genomes

AF:

0.0000433

AC:

AN:

69302

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000901

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000162

AC:

AN:

1235804

Hom.:

Cov.:

AF XY:

0.00000164

AC XY:

AN XY:

611234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27322

American (AMR)

AF:

0.00

AC:

AN:

34242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19548

East Asian (EAS)

AF:

0.00

AC:

AN:

16250

South Asian (SAS)

AF:

0.00

AC:

AN:

68072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4922

European-Non Finnish (NFE)

AF:

0.00000203

AC:

AN:

984580

Other (OTH)

AF:

0.00

AC:

AN:

46656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000433

AC:

AN:

69302

Hom.:

Cov.:

AF XY:

0.0000594

AC XY:

AN XY:

33698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19470

American (AMR)

AF:

0.00

AC:

AN:

5854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1786

East Asian (EAS)

AF:

0.00

AC:

AN:

1318

South Asian (SAS)

AF:

0.00

AC:

AN:

1490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4476

Middle Eastern (MID)

AF:

0.00

AC:

AN:

180

European-Non Finnish (NFE)

AF:

0.0000901

AC:

AN:

33282

Other (OTH)

AF:

0.00

AC:

AN:

994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000302

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.058

Eigen_PC

Benign

0.077

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.017

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

PhyloP100

3.5

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.3

REVEL

Benign

0.098

Sift

Benign

0.10

Sift4G

Benign

0.25

Vest4

0.43

MutPred

0.47

Gain of catalytic residue at Q412 (P = 0.0914)

MVP

0.33

MPC

0.084

ClinPred

0.28

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.59

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over